{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T01:42:11Z","timestamp":1791164531314,"version":"4.1.0"},"reference-count":168,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2009,3,1]],"date-time":"2009-03-01T00:00:00Z","timestamp":1235865600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2009,3,1]],"date-time":"2009-03-01T00:00:00Z","timestamp":1235865600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2009,3,1]],"date-time":"2009-03-01T00:00:00Z","timestamp":1235865600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2009,3,1]],"date-time":"2009-03-01T00:00:00Z","timestamp":1235865600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2009,3,1]],"date-time":"2009-03-01T00:00:00Z","timestamp":1235865600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2009,3,1]],"date-time":"2009-03-01T00:00:00Z","timestamp":1235865600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2009,3,1]],"date-time":"2009-03-01T00:00:00Z","timestamp":1235865600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","internationaljournalofcardiology.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["International Journal of Cardiology"],"published-print":{"date-parts":[[2009,3]]},"DOI":"10.1016\/j.ijcard.2008.12.196","type":"journal-article","created":{"date-parts":[[2009,2,1]],"date-time":"2009-02-01T04:11:43Z","timestamp":1233461503000},"page":"318-336","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":61,"title":["Pacemaker activity of the human sinoatrial node: Role of the hyperpolarization-activated current, If"],"prefix":"10.1016","volume":"132","author":[{"given":"Arie O.","family":"Verkerk","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoni C.G.","family":"van Ginneken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Wilders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ijcard.2008.12.196_bib1","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1152\/physrev.1993.73.1.197","article-title":"Cardiac pacemaking in the sinoatrial node","volume":"73","author":"Irisawa","year":"1993","journal-title":"Physiol Rev"},{"key":"10.1016\/j.ijcard.2008.12.196_bib2","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/S0008-6363(00)00135-8","article-title":"The sinoatrial node, a heterogeneous pacemaker structure","volume":"47","author":"Boyett","year":"2000","journal-title":"Cardiovasc Res"},{"key":"10.1016\/j.ijcard.2008.12.196_bib3","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1540\/jsmr.39.175","article-title":"Sino-atrial nodal cells of mammalian hearts: ionic currents and gene expression of pacemaker ionic channels","volume":"39","author":"Satoh","year":"2003","journal-title":"J Smooth Muscle Res"},{"key":"10.1016\/j.ijcard.2008.12.196_bib4","doi-asserted-by":"crossref","first-page":"169","DOI":"10.2174\/187152906778249572","article-title":"Physiological and pharmacological insights into the role of ionic channels in cardiac pacemaker activity","volume":"6","author":"Couette","year":"2006","journal-title":"Cardiovasc Hematol Disord Drug Targets"},{"key":"10.1016\/j.ijcard.2008.12.196_bib5","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1161\/CIRCULATIONAHA.106.616011","article-title":"New insights into pacemaker activity: promoting understanding of sick sinus syndrome","volume":"115","author":"Dobrzynski","year":"2007","journal-title":"Circulation"},{"key":"10.1016\/j.ijcard.2008.12.196_bib6","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.hlc.2007.07.005","article-title":"Normal heart rhythm is initiated and regulated by an intracellular calcium clock within pacemaker cells","volume":"16","author":"Maltsev","year":"2007","journal-title":"Heart Lung Circ"},{"key":"10.1016\/j.ijcard.2008.12.196_bib7","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1152\/physrev.00018.2007","article-title":"Genesis and regulation of the heart automaticity","volume":"88","author":"Mangoni","year":"2008","journal-title":"Physiol Rev"},{"key":"10.1016\/j.ijcard.2008.12.196_bib8","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1113\/jphysiol.1980.sp013474","article-title":"Voltage-clamp investigations of membrane currents underlying pace-maker activity in rabbit sinoatrial node","volume":"308","author":"Brown","year":"1980","journal-title":"J Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib9","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/351145a0","article-title":"Direct activation of cardiac pacemaker channels by intracellular cyclic AMP","volume":"351","author":"DiFrancesco","year":"1991","journal-title":"Nature"},{"key":"10.1016\/j.ijcard.2008.12.196_bib10","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/280235a0","article-title":"How does adrenaline accelerate the heart?","volume":"280","author":"Brown","year":"1979","journal-title":"Nature"},{"key":"10.1016\/j.ijcard.2008.12.196_bib11","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/285228a0","article-title":"Slow current systems in the A\u2013V node of the rabbit heart","volume":"285","author":"Noma","year":"1980","journal-title":"Nature"},{"key":"10.1016\/j.ijcard.2008.12.196_bib12","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1113\/jphysiol.1981.sp013714","article-title":"A study of the ionic nature of the pace-maker current in calf Purkinje fibres","volume":"314","author":"DiFrancesco","year":"1981","journal-title":"J Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib13","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.pbiomolbio.2005.05.001","article-title":"Serious workings of the funny current","volume":"90","author":"DiFrancesco","year":"2006","journal-title":"Prog Biophys Mol Biol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib14","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1007\/BF00584356","article-title":"Does the \u201cpacemaker current\u201d generate the diastolic depolarization in the rabbit SA node cells?","volume":"397","author":"Noma","year":"1983","journal-title":"Pfl\u00fcgers Arch"},{"key":"10.1016\/j.ijcard.2008.12.196_bib15","first-page":"101","article-title":"Intracellular Ca2+ release sparks atrial pacemaker activity","volume":"16","author":"Lipsius","year":"2001","journal-title":"News Physiol Sci"},{"key":"10.1016\/j.ijcard.2008.12.196_bib16","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/S0008-6363(95)00028-3","article-title":"The pacemaker current (If) does not play an important role in regulating SA node pacemaker activity","volume":"30","author":"Vassalle","year":"1995","journal-title":"Cardiovasc Res"},{"key":"10.1016\/j.ijcard.2008.12.196_bib17","doi-asserted-by":"crossref","first-page":"4423","DOI":"10.1038\/sj.emboj.7601868","article-title":"HCN4 provides a \u2018depolarization reserve\u2019 and is not required for heart rate acceleration in mice","volume":"26","author":"Herrmann","year":"2007","journal-title":"EMBO J"},{"key":"10.1016\/j.ijcard.2008.12.196_bib18","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1038\/emboj.2008.3","article-title":"Cardiac pacemaker function of HCN4 channels in mice is confined to embryonic development and requires cyclic AMP","volume":"27","author":"Harzheim","year":"2008","journal-title":"EMBO J"},{"key":"10.1016\/j.ijcard.2008.12.196_bib19","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0008-6363(99)00322-3","article-title":"The normal range and determinants of the intrinsic heart rate in man","volume":"45","author":"Opthof","year":"2000","journal-title":"Cardiovasc Res"},{"key":"10.1016\/j.ijcard.2008.12.196_bib20","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/S0896-6273(00)80508-5","article-title":"Not so funny anymore: pacing channels are cloned","volume":"21","author":"Clapham","year":"1998","journal-title":"Neuron"},{"key":"10.1016\/j.ijcard.2008.12.196_bib21","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/S0092-8674(00)81434-8","article-title":"Identification of a gene encoding a hyperpolarization-activated pacemaker channel of brain","volume":"93","author":"Santoro","year":"1998","journal-title":"Cell"},{"key":"10.1016\/j.ijcard.2008.12.196_bib22","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/31248","article-title":"Molecular identification of a hyperpolarization-activated channel in sea urchin sperm","volume":"393","author":"Gauss","year":"1998","journal-title":"Nature"},{"key":"10.1016\/j.ijcard.2008.12.196_bib23","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/31255","article-title":"A family of hyperpolarization-activated mammalian cation channels","volume":"393","author":"Ludwig","year":"1998","journal-title":"Nature"},{"key":"10.1016\/j.ijcard.2008.12.196_bib24","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1152\/physiolgenomics.00142.2006","article-title":"Evolution and structural diversification of hyperpolarization-activated cyclic nucleotide-gated channel genes","volume":"29","author":"Jackson","year":"2007","journal-title":"Physiol Genomics"},{"key":"10.1016\/j.ijcard.2008.12.196_bib25","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/S1050-1738(02)00162-7","article-title":"Cardiac HCN channels: structure, function, and modulation","volume":"12","author":"Biel","year":"2002","journal-title":"Trends Cardiovasc Med"},{"key":"10.1016\/j.ijcard.2008.12.196_bib26","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0896-6273(04)00199-0","article-title":"Quickening the pace: looking into the heart of HCN channels","volume":"42","author":"Rosenbaum","year":"2004","journal-title":"Neuron"},{"key":"10.1016\/j.ijcard.2008.12.196_bib27","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1113\/jphysiol.2002.027698","article-title":"Heteromeric HCN1\u2013HCN4 channels: a comparison with native pacemaker channels from the rabbit sinoatrial node","volume":"549","author":"Altomare","year":"2003","journal-title":"J Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib28","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1161\/01.CIR.0000153799.65783.3A","article-title":"Single-channel properties support a potential contribution of hyperpolarization-activated cyclic nucleotide-gated channels and If to cardiac arrhythmias","volume":"111","author":"Michels","year":"2005","journal-title":"Circulation"},{"key":"10.1016\/j.ijcard.2008.12.196_bib29","doi-asserted-by":"crossref","first-page":"22900","DOI":"10.1074\/jbc.M610978200","article-title":"HCN2 and HCN4 isoforms self-assemble and co-assemble with equal preference to form functional pacemaker channels","volume":"282","author":"Whitaker","year":"2007","journal-title":"J Biol Chem"},{"key":"10.1016\/j.ijcard.2008.12.196_bib30","doi-asserted-by":"crossref","first-page":"e84","DOI":"10.1161\/hh1201.093511","article-title":"MinK-related peptide 1: a \u03b2 subunit for the HCN ion channel subunit family enhances expression and speeds activation","volume":"88","author":"Yu","year":"2001","journal-title":"Circ Res"},{"key":"10.1016\/j.ijcard.2008.12.196_bib31","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1007\/s00424-003-1127-7","article-title":"KCNE2 modulates current amplitudes and activation kinetics of HCN4: influence of KCNE family members on HCN4 currents","volume":"446","author":"Decher","year":"2003","journal-title":"Pfl\u00fcgers Arch"},{"key":"10.1016\/j.ijcard.2008.12.196_bib32","doi-asserted-by":"crossref","first-page":"43497","DOI":"10.1074\/jbc.M405018200","article-title":"MiRP1 modulates HCN2 channel expression and gating in cardiac myocytes","volume":"279","author":"Qu","year":"2004","journal-title":"J Biol Chem"},{"key":"10.1016\/j.ijcard.2008.12.196_bib33","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1161\/01.RES.85.1.e1","article-title":"Distribution and prevalence of hyperpolarization-activated cation channel (HCN) mRNA expression in cardiac tissue","volume":"85","author":"Shi","year":"1999","journal-title":"Circ Res"},{"key":"10.1016\/j.ijcard.2008.12.196_bib34","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1161\/01.RES.0000039534.18114.D9","article-title":"Comparison of ion-channel subunit expression in canine cardiac Purkinje fibers and ventricular muscle","volume":"91","author":"Han","year":"2002","journal-title":"Circ Res"},{"key":"10.1016\/j.ijcard.2008.12.196_bib35","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1113\/jphysiol.2004.074047","article-title":"Specific pattern of ionic channel gene expression associated with pacemaker activity in the mouse heart","volume":"562","author":"Marionneau","year":"2005","journal-title":"J Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib36","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1046\/j.1432-1327.2001.02036.x","article-title":"Cellular expression and functional characterization of four hyperpolarization-activated pacemaker channels in cardiac and neuronal tissues","volume":"268","author":"Moosmang","year":"2001","journal-title":"Eur J Biochem"},{"key":"10.1016\/j.ijcard.2008.12.196_bib37","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.cardiores.2005.02.011","article-title":"Sinus node dysfunction and hyperpolarization-activated (HCN) channel subunit remodeling in a canine heart failure model","volume":"66","author":"Zicha","year":"2005","journal-title":"Cardiovasc Res"},{"key":"10.1016\/j.ijcard.2008.12.196_bib38","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1007\/s00395-007-0660-5","article-title":"Age-related down-regulation of HCN channels in rat sinoatrial node","volume":"102","author":"Huang","year":"2007","journal-title":"Basic Res Cardiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib39","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1161\/01.RES.0000251717.98379.69","article-title":"Differential expression of ion channel transcripts in atrial muscle and sinoatrial node in rabbit","volume":"99","author":"Tellez","year":"2006","journal-title":"Circ Res"},{"key":"10.1016\/j.ijcard.2008.12.196_bib40","first-page":"H1549","article-title":"Properties and modulation of If in newborn versus adult cardiac SA node","volume":"272","author":"Accili","year":"1997","journal-title":"Am J Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib41","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1113\/jphysiol.2003.041954","article-title":"Regional distribution of hyperpolarization-activated current (If) and hyperpolarization-activated cyclic nucleotide-gated channel mRNA expression in ventricular cells from control and hypertrophied rat hearts","volume":"553","author":"Fern\u00e1ndez-Velasco","year":"2003","journal-title":"J Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib42","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1161\/01.CIR.0000083719.51661.B9","article-title":"Ionic remodeling of sinoatrial node cells by heart failure","volume":"108","author":"Verkerk","year":"2003","journal-title":"Circulation"},{"key":"10.1016\/j.ijcard.2008.12.196_bib43","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1113\/jphysiol.2006.126714","article-title":"Regional and tissue specific transcript signatures of ion channel genes in the non-diseased human heart","volume":"582","author":"Gaborit","year":"2007","journal-title":"J Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib44","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.yjmcc.2008.04.013","article-title":"Molecular basis of funny current (If) in normal and failing human heart","volume":"45","author":"Stillitano","year":"2008","journal-title":"J Mol Cell Cardiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib45","doi-asserted-by":"crossref","first-page":"9391","DOI":"10.1073\/pnas.96.16.9391","article-title":"Molecular characterization of a slowly gating human hyperpolarization-activated channel predominantly expressed in thalamus, heart, and testis","volume":"96","author":"Seifert","year":"1999","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.ijcard.2008.12.196_bib46","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.1172\/JCI200316387","article-title":"Pacemaker channel dysfunction in a patient with sinus node disease","volume":"111","author":"Schulze-Bahr","year":"2003","journal-title":"J Clin Invest"},{"key":"10.1016\/j.ijcard.2008.12.196_bib47","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1113\/jphysiol.1980.sp013475","article-title":"Properties of the current if in the sino-atrial node of the rabbit compared with those of the current iK2 in Purkinje fibres","volume":"308","author":"DiFrancesco","year":"1980","journal-title":"J Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib48","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1113\/jphysiol.1983.sp014631","article-title":"The kinetics and temperature dependence of the pace-maker current if in sheep Purkinje fibres","volume":"337","author":"Hart","year":"1983","journal-title":"J Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib49","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1529\/biophysj.106.092478","article-title":"Dual stretch responses of mHCN2 pacemaker channels: accelerated activation, accelerated deactivation","volume":"92","author":"Lin","year":"2007","journal-title":"Biophys J"},{"key":"10.1016\/j.ijcard.2008.12.196_bib50","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1113\/jphysiol.1989.sp017488","article-title":"Modulation by intracellular Ca2+ of the hyperpolarization-activated inward current in rabbit single sino-atrial node cells","volume":"409","author":"Hagiwara","year":"1989","journal-title":"J Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib51","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1113\/jphysiol.1992.sp019230","article-title":"Control of the hyperpolarization-activated cation current by external anions in rabbit sino-atrial node cells","volume":"453","author":"Frace","year":"1992","journal-title":"J Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib52","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1038\/35098087","article-title":"Hyperpolarization-activated channels HCN1 and HCN4 mediate responses to sour stimuli","volume":"413","author":"Stevens","year":"2001","journal-title":"Nature"},{"key":"10.1016\/j.ijcard.2008.12.196_bib53","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0005-2736(02)00687-9","article-title":"Protons and calcium alter gating of the hyperpolarization-activated cation current (Ih) in rod photoreceptors","volume":"1609","author":"Malcolm","year":"2003","journal-title":"Biochim Biophys Acta"},{"key":"10.1016\/j.ijcard.2008.12.196_bib54","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0008-6363(02)00668-5","article-title":"Modulation of the hyperpolarization-activated current (If) by calcium and calmodulin in the guinea-pig sino-atrial node","volume":"57","author":"Rigg","year":"2003","journal-title":"Cardiovasc Res"},{"key":"10.1016\/j.ijcard.2008.12.196_bib55","doi-asserted-by":"crossref","first-page":"13694","DOI":"10.1074\/jbc.M413197200","article-title":"An arginine residue in the pore region is a key determinant of chloride dependence in cardiac pacemaker channels","volume":"280","author":"Wahl-Schott","year":"2005","journal-title":"J Biol Chem"},{"key":"10.1016\/j.ijcard.2008.12.196_bib56","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1007\/s00424-006-0095-0","article-title":"The enhancement of HCN channel instantaneous current facilitated by slow deactivation is regulated by intracellular chloride concentration","volume":"452","author":"Mistrik","year":"2006","journal-title":"Pfl\u00fcgers Arch"},{"key":"10.1016\/j.ijcard.2008.12.196_bib57","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1038\/35081088","article-title":"Molecular mechanism of cAMP modulation of HCN pacemaker channels","volume":"411","author":"Wainger","year":"2001","journal-title":"Nature"},{"key":"10.1016\/j.ijcard.2008.12.196_bib58","doi-asserted-by":"crossref","first-page":"e8","DOI":"10.1161\/hh1301.094395","article-title":"HCN2 overexpression in newborn and adult ventricular myocytes: distinct effects on gating and excitability","volume":"89","author":"Qu","year":"2001","journal-title":"Circ Res"},{"key":"10.1016\/j.ijcard.2008.12.196_bib59","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1007\/s00424-002-0860-7","article-title":"Functional comparison of HCN isoforms expressed in ventricular and HEK 293 cells","volume":"444","author":"Qu","year":"2002","journal-title":"Pfl\u00fcgers Arch"},{"key":"10.1016\/j.ijcard.2008.12.196_bib60","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1002\/jgm.1172","article-title":"Engineering physiologically controlled pacemaker cells with lentiviral HCN4 gene transfer","volume":"10","author":"Boink","year":"2008","journal-title":"J Gene Med"},{"key":"10.1016\/j.ijcard.2008.12.196_bib61","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1113\/jphysiol.1986.sp016177","article-title":"Properties of the hyperpolarizing-activated current (if) in cells isolated from the rabbit sino-atrial node","volume":"377","author":"DiFrancesco","year":"1986","journal-title":"J Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib62","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1113\/jphysiol.1991.sp018459","article-title":"Voltage clamp measurements of the hyperpolarization-activated inward current If in single cells from rabbit sino-atrial node","volume":"434","author":"van Ginneken","year":"1991","journal-title":"J Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib63","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1111\/j.1469-7793.2001.0093k.x","article-title":"Determinants of activation kinetics in mammalian hyperpolarization-activated cation channels","volume":"537","author":"Ishii","year":"2001","journal-title":"J Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib64","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1113\/jphysiol.1984.sp015114","article-title":"Characterization of the pace-maker current kinetics in calf Purkinje fibres","volume":"348","author":"DiFrancesco","year":"1984","journal-title":"J Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib65","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1085\/jgp.200409130","article-title":"Hysteresis in the voltage dependence of HCN channels: conversion between two modes affects pacemaker properties","volume":"125","author":"M\u00e4nnikk\u00f6","year":"2005","journal-title":"J Gen Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib66","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1113\/jphysiol.2006.110437","article-title":"Mode shifts in the voltage gating of the mouse and human HCN2 and HCN4 channels","volume":"575","author":"Elinder","year":"2006","journal-title":"J Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib67","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/j.bbrc.2007.05.127","article-title":"Peripheral N- and C-terminal domains determine deactivation kinetics of HCN channels","volume":"359","author":"Ishii","year":"2007","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.ijcard.2008.12.196_bib68","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1016\/j.cardiores.2005.04.001","article-title":"Supraventricular pacemaker activity in the canine heart: contributions from HCN channels in control conditions and in a model of heart failure","volume":"66","author":"Giles","year":"2005","journal-title":"Cardiovasc Res"},{"key":"10.1016\/j.ijcard.2008.12.196_bib69","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1113\/jphysiol.1981.sp013713","article-title":"A new interpretation of the pace-maker current in calf Purkinje fibres","volume":"314","author":"DiFrancesco","year":"1981","journal-title":"J Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib70","doi-asserted-by":"crossref","first-page":"C1147","DOI":"10.1152\/ajpcell.00598.2005","article-title":"Calcium influx through If channels in rat ventricular myocytes","volume":"292","author":"Yu","year":"2007","journal-title":"Am J Physiol Cell Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib71","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1093\/cvr\/cvn032","article-title":"Direct evidence for calcium conductance of hyperpolarization-activated cyclic nucleotide-gated channels and human native If at physiological calcium concentrations","volume":"78","author":"Michels","year":"2008","journal-title":"Cardiovasc Res"},{"key":"10.1016\/j.ijcard.2008.12.196_bib72","doi-asserted-by":"crossref","first-page":"5101","DOI":"10.1074\/jbc.M106974200","article-title":"Pacemaker channels produce an instantaneous current","volume":"277","author":"Proenza","year":"2002","journal-title":"J Biol Chem"},{"key":"10.1016\/j.ijcard.2008.12.196_bib73","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1111\/j.1540-8167.1996.tb00479.x","article-title":"\u03b2-Adrenergic and muscarinic cholinergic receptor densities in the human sinoatrial node: identification of a high \u03b22-adrenergic receptor density","volume":"7","author":"Rodefeld","year":"1996","journal-title":"J Cardiovasc Electrophysiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib74","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.yjmcc.2006.09.018","article-title":"Localization of f-channels to caveolae mediates specific \u03b22-adrenergic receptor modulation of rate in sinoatrial myocytes","volume":"42","author":"Barbuti","year":"2007","journal-title":"J Mol Cell Cardiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib75","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1007\/s003950170003","article-title":"Presence, distribution and physiological function of adrenergic and muscarinic receptor subtypes in the human heart","volume":"96","author":"Brodde","year":"2001","journal-title":"Basic Res Cardiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib76","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s00210-008-0285-8","article-title":"The detection of the non-M2 muscarinic receptor subtype in the rat heart atria and ventricles","volume":"378","author":"Myslivecek","year":"2008","journal-title":"Naunyn Schmiedebergs Arch Pharmacol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib77","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.pharmthera.2005.01.005","article-title":"Physiology and pharmacology of the cardiac pacemaker (\u201cfunny\u201d) current","volume":"107","author":"Baruscotti","year":"2005","journal-title":"Pharmacol Ther"},{"key":"10.1016\/j.ijcard.2008.12.196_bib78","doi-asserted-by":"crossref","first-page":"29930","DOI":"10.1074\/jbc.M103971200","article-title":"C terminus-mediated control of voltage and cAMP gating of hyperpolarization-activated cyclic nucleotide-gated channels","volume":"276","author":"Viscomi","year":"2001","journal-title":"J Biol Chem"},{"key":"10.1016\/j.ijcard.2008.12.196_bib79","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1085\/jgp.118.3.237","article-title":"Regulation of hyperpolarization-activated HCN channel gating and cAMP modulation due to interactions of COOH terminus and core transmembrane regions","volume":"118","author":"Wang","year":"2001","journal-title":"J Gen Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib80","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1113\/jphysiol.1992.sp019029","article-title":"Background current in sino-atrial node cells of the rabbit heart","volume":"448","author":"Hagiwara","year":"1992","journal-title":"J Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib81","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1098\/rspb.1992.0150","article-title":"Reciprocal role of the inward currents ib,Na and if in controlling and stabilizing pacemaker frequency of rabbit sino-atrial node cells","volume":"250","author":"Noble","year":"1992","journal-title":"Proc R Soc Lond B Biol Sci"},{"key":"10.1016\/j.ijcard.2008.12.196_bib82","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1113\/jphysiol.1995.sp020563","article-title":"A sustained inward current activated at the diastolic potential range in rabbit sino-atrial node cells","volume":"483","author":"Guo","year":"1995","journal-title":"J Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib83","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1161\/01.RES.87.2.88","article-title":"Sustained inward current during pacemaker depolarization in mammalian sinoatrial node cells","volume":"87","author":"Mitsuiye","year":"2000","journal-title":"Circ Res"},{"key":"10.1016\/j.ijcard.2008.12.196_bib84","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1113\/jphysiol.1988.sp016916","article-title":"Contribution of two types of calcium currents to the pacemaker potentials of rabbit sino-atrial node cells","volume":"395","author":"Hagiwara","year":"1988","journal-title":"J Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib85","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1007\/BF00581808","article-title":"Calcium currents in single SA nodal cells of the rabbit heart studied with action potential clamp","volume":"413","author":"Doerr","year":"1989","journal-title":"Pfl\u00fcgers Arch"},{"key":"10.1016\/j.ijcard.2008.12.196_bib86","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1161\/hh1201.092095","article-title":"Sinoatrial nodal cell ryanodine receptor and Na+\u2013Ca2+ exchanger: molecular partners in pacemaker regulation","volume":"88","author":"Bogdanov","year":"2001","journal-title":"Circ Res"},{"key":"10.1016\/j.ijcard.2008.12.196_bib87","first-page":"H453","article-title":"Role of rapidly activating delayed rectifier K+ current in sinoatrial node pacemaker activity","volume":"269","author":"Ono","year":"1995","journal-title":"Am J Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib88","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1161\/01.RES.76.4.607","article-title":"Effects of delayed rectifier current blockade by E-4031 on impulse generation in single sinoatrial nodal myocytes of the rabbit","volume":"76","author":"Verheijck","year":"1995","journal-title":"Circ Res"},{"key":"10.1016\/j.ijcard.2008.12.196_bib89","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/S0008-6363(01)00459-X","article-title":"Role of the 293b-sensitive, slowly activating delayed rectifier potassium current, iKs, in pacemaker activity of rabbit isolated sino-atrial node cells","volume":"53","author":"Lei","year":"2002","journal-title":"Cardiovasc Res"},{"key":"10.1016\/j.ijcard.2008.12.196_bib90","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1113\/jphysiol.2001.016741","article-title":"Rapidly and slowly activating components of delayed rectifier K+ current in guinea-pig sino-atrial node pacemaker cells","volume":"540","author":"Matsuura","year":"2002","journal-title":"J Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib91","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1038\/303250a0","article-title":"Acetylcholine activation of single muscarinic K+ channels in isolated pacemaker cells of the mammalian heart","volume":"303","author":"Sakmann","year":"1983","journal-title":"Nature"},{"key":"10.1016\/j.ijcard.2008.12.196_bib92","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1113\/jphysiol.1990.sp018264","article-title":"Pacemaking in rabbit isolated sino-atrial node cells during Cs+ block of the hyperpolarization-activated current if","volume":"429","author":"Denyer","year":"1990","journal-title":"J Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib93","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1113\/jphysiol.1991.sp018457","article-title":"The contribution of the \u2018pacemaker\u2019 current (if) to generation of spontaneous activity in rabbit sino-atrial node myocytes","volume":"434","author":"DiFrancesco","year":"1991","journal-title":"J Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib94","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1046\/j.1540-8167.2002.01303.x","article-title":"Are we lost in the labyrinth of the sinoatrial node pacemaker mechanism?","volume":"13","author":"Kodama","year":"2002","journal-title":"J Cardiovasc Electrophysiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib95","doi-asserted-by":"crossref","first-page":"e41","DOI":"10.1161\/01.RES.0000055904.21974.BE","article-title":"Sarcoplasmic reticulum Ca2+ release is not a dominating factor in sinoatrial node pacemaker activity","volume":"92","author":"Honjo","year":"2003","journal-title":"Circ Res"},{"key":"10.1016\/j.ijcard.2008.12.196_bib96","doi-asserted-by":"crossref","first-page":"e45","DOI":"10.1161\/01.RES.0000055920.64384.FB","article-title":"Cyclic variation of intracellular calcium: a critical factor for cardiac pacemaker cell dominance","volume":"92","author":"Lakatta","year":"2003","journal-title":"Circ Res"},{"key":"10.1016\/j.ijcard.2008.12.196_bib97","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/s11517-006-0060-2","article-title":"Biological pacemakers based on If","volume":"45","author":"Rosen","year":"2007","journal-title":"Med Biol Eng Comput"},{"key":"10.1016\/j.ijcard.2008.12.196_bib98","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1093\/cvr\/19.5.304","article-title":"Electrophysiological study of the two main pacemaker mechanisms in the rabbit sinus node","volume":"19","author":"Kreitner","year":"1985","journal-title":"Cardiovasc Res"},{"key":"10.1016\/j.ijcard.2008.12.196_bib99","first-page":"H2782","article-title":"Variation in effects of Cs+, UL-FS-49, and ZD-7288 within sinoatrial node","volume":"272","author":"Nikmaram","year":"1997","journal-title":"Am J Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib100","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1113\/jphysiol.1996.sp021728","article-title":"Correlation between electrical activity and the size of rabbit sinoatrial node cells","volume":"496","author":"Honjo","year":"1996","journal-title":"J Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib101","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1016\/S0006-3495(86)83559-7","article-title":"Propagation through electrically coupled cells: how a small SA node drives a large atrium","volume":"50","author":"Joyner","year":"1986","journal-title":"Biophys J"},{"key":"10.1016\/j.ijcard.2008.12.196_bib102","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s004240000413","article-title":"Effects of anisotropy on the development of cardiac arrhythmias associated with focal activity","volume":"441","author":"Wilders","year":"2000","journal-title":"Pfl\u00fcgers Arch"},{"key":"10.1016\/j.ijcard.2008.12.196_bib103","series-title":"Proceedings of the 1994 Conference on Supercomputing","first-page":"560","article-title":"Factors controlling generation and propagation of pacemaker potentials in network models of mammalian SA node","author":"Winslow","year":"1994"},{"key":"10.1016\/j.ijcard.2008.12.196_bib104","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1146\/annurev.me.30.020179.000515","article-title":"Sick sinus syndrome","volume":"30","author":"Bigger","year":"1979","journal-title":"Annu Rev Med"},{"key":"10.1016\/j.ijcard.2008.12.196_bib105","doi-asserted-by":"crossref","first-page":"1854","DOI":"10.1056\/NEJMoa013040","article-title":"Ventricular pacing or dual-chamber pacing for sinus-node dysfunction","volume":"346","author":"Lamas","year":"2002","journal-title":"N Engl J Med"},{"key":"10.1016\/j.ijcard.2008.12.196_bib106","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1056\/NEJM200003093421006","article-title":"The evaluation and management of bradycardia","volume":"342","author":"Mangrum","year":"2000","journal-title":"N Engl J Med"},{"key":"10.1016\/j.ijcard.2008.12.196_bib107","first-page":"1725","article-title":"Diagnosis and treatment of sick sinus syndrome","volume":"67","author":"Ad\u00e1n","year":"2003","journal-title":"Am Fam Physician"},{"key":"10.1016\/j.ijcard.2008.12.196_bib108","doi-asserted-by":"crossref","first-page":"27194","DOI":"10.1074\/jbc.M311953200","article-title":"Functional characterization of a trafficking-defective HCN4 mutation, D553N, associated with cardiac arrhythmia","volume":"279","author":"Ueda","year":"2004","journal-title":"J Biol Chem"},{"key":"10.1016\/j.ijcard.2008.12.196_bib109","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1056\/NEJMoa052475","article-title":"Familial sinus bradycardia associated with a mutation in the cardiac pacemaker channel","volume":"354","author":"Milanesi","year":"2006","journal-title":"N Engl J Med"},{"key":"10.1016\/j.ijcard.2008.12.196_bib110","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1161\/CIRCULATIONAHA.107.706887","article-title":"Point mutation in the HCN4 cardiac ion channel pore affecting synthesis, trafficking, and functional expression is associated with familial asymptomatic sinus bradycardia","volume":"116","author":"Nof","year":"2007","journal-title":"Circulation"},{"key":"10.1016\/j.ijcard.2008.12.196_bib111","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1111\/j.1540-8167.1997.tb00788.x","article-title":"Electrophysiologic properties of the adult human sinus node","volume":"8","author":"Drouin","year":"1997","journal-title":"J Cardiovasc Electrophysiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib112","doi-asserted-by":"crossref","first-page":"2472","DOI":"10.1093\/eurheartj\/ehm339","article-title":"Pacemaker current (If) in the human sinoatrial node","volume":"28","author":"Verkerk","year":"2007","journal-title":"Eur Heart J"},{"key":"10.1016\/j.ijcard.2008.12.196_bib113","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0008-6363(01)00417-5","article-title":"Function and structure of the mouse sinus node: nothing you can see that isn\u2019t shown","volume":"52","author":"Opthof","year":"2001","journal-title":"Cardiovasc Res"},{"key":"10.1016\/j.ijcard.2008.12.196_bib114","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1161\/01.CIR.0000139336.69955.AB","article-title":"Remodeling of sinus node function in patients with congestive heart failure: reduction in sinus node reserve","volume":"110","author":"Sanders","year":"2004","journal-title":"Circulation"},{"key":"10.1016\/j.ijcard.2008.12.196_bib115","doi-asserted-by":"crossref","first-page":"2975","DOI":"10.1161\/01.CIR.101.25.2975","article-title":"Changes in sinus node function in a rabbit model of heart failure with ventricular arrhythmias and sudden death","volume":"101","author":"Opthof","year":"2000","journal-title":"Circulation"},{"key":"10.1016\/j.ijcard.2008.12.196_bib116","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1113\/jphysiol.1990.sp018219","article-title":"Rabbit sino-atrial node cells: isolation and electrophysiological properties","volume":"428","author":"Denyer","year":"1990","journal-title":"J Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib117","doi-asserted-by":"crossref","first-page":"H1232","DOI":"10.1152\/ajpheart.2001.280.3.H1232","article-title":"Morphological and membrane characteristics of spider and spindle cells isolated from rabbit sinus node","volume":"280","author":"Wu","year":"2001","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib118","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S0008-6363(01)00370-4","article-title":"Properties of the hyperpolarization-activated current (If) in isolated mouse sino-atrial cells","volume":"52","author":"Mangoni","year":"2001","journal-title":"Cardiovasc Res"},{"key":"10.1016\/j.ijcard.2008.12.196_bib119","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1007\/s004240050293","article-title":"The sustained inward current in sino-atrial node cells of guinea-pig heart","volume":"433","author":"Guo","year":"1997","journal-title":"Pfl\u00fcgers Arch"},{"key":"10.1016\/j.ijcard.2008.12.196_bib120","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1161\/01.RES.82.5.604","article-title":"Differential expression of gap junction proteins in the canine sinus node","volume":"82","author":"Kwong","year":"1998","journal-title":"Circ Res"},{"key":"10.1016\/j.ijcard.2008.12.196_bib121","first-page":"904","article-title":"Single cells isolated from human sinoatrial node: action potentials and numerical reconstruction of pacemaker current","volume":"2007","author":"Verkerk","year":"2007","journal-title":"Conf Proc IEEE Eng Med Biol Soc"},{"key":"10.1016\/j.ijcard.2008.12.196_bib122","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1540\/jsmr.39.195","article-title":"Pacemaker mechanism of porcine sino-atrial node cells","volume":"39","author":"Ono","year":"2003","journal-title":"J Smooth Muscle Res"},{"key":"10.1016\/j.ijcard.2008.12.196_bib123","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/s11517-006-0127-0","article-title":"Computer modelling of the sinoatrial node","volume":"45","author":"Wilders","year":"2007","journal-title":"Med Biol Eng Comput"},{"key":"10.1016\/j.ijcard.2008.12.196_bib124","doi-asserted-by":"crossref","first-page":"133","DOI":"10.2165\/00003495-200666020-00001","article-title":"Impact of increased heart rate on clinical outcomes in hypertension: implications for antihypertensive drug therapy","volume":"66","author":"Palatini","year":"2006","journal-title":"Drugs"},{"key":"10.1016\/j.ijcard.2008.12.196_bib125","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/ncpcardio0052","article-title":"Drug insight: If inhibitors as specific heart-rate-reducing agents","volume":"1","author":"Borer","year":"2004","journal-title":"Nature Clin Practice Cardiovasc Med"},{"issue":"Suppl 2","key":"10.1016\/j.ijcard.2008.12.196_bib126","doi-asserted-by":"crossref","first-page":"15","DOI":"10.2165\/00003495-200767002-00003","article-title":"The funny current: cellular basis for the control of heart rate","volume":"67","author":"DiFrancesco","year":"2007","journal-title":"Drugs"},{"key":"10.1016\/j.ijcard.2008.12.196_bib127","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1161\/01.CIR.88.5.2389","article-title":"Use-dependent block of the pacemaker current If in rabbit sinoatrial node cells by zatebradine (UL-FS 49). On the mode of action of sinus node inhibitors","volume":"88","author":"Goethals","year":"1993","journal-title":"Circulation"},{"key":"10.1016\/j.ijcard.2008.12.196_bib128","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.ejphar.2003.08.083","article-title":"Use-dependent blockade of cardiac pacemaker current (If) by cilobradine and zatebradine","volume":"478","author":"van Bogaert","year":"2003","journal-title":"Eur J Pharmacol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib129","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/BF00581900","article-title":"Alinidine modifies the pacemaker current in sheep Purkinje fibers","volume":"410","author":"Snyders","year":"1987","journal-title":"Pfl\u00fcgers Arch"},{"key":"10.1016\/j.ijcard.2008.12.196_bib130","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1111\/j.1476-5381.1993.tb13815.x","article-title":"Inhibitory actions of ZENECA ZD7288 on whole-cell hyperpolarization activated inward current (If) in guinea-pig dissociated sinoatrial node cells","volume":"110","author":"BoSmith","year":"1993","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib131","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s004240050488","article-title":"Action of the hyperpolarization-activated current (Ih) blocker ZD 7288 in hippocampal CA1 neurons","volume":"435","author":"Gasparini","year":"1997","journal-title":"Pfl\u00fcgers Arch"},{"key":"10.1016\/j.ijcard.2008.12.196_bib132","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1111\/j.1476-5381.1994.tb13025.x","article-title":"Electrophysiological effects of S 16257, a novel sino-atrial node modulator, on rabbit and guinea-pig cardiac preparations: comparison with UL-FS 49","volume":"112","author":"Thollon","year":"1994","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib133","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1111\/j.1476-5381.1996.tb15505.x","article-title":"Mode of action of bradycardic agent, S 16257, on ionic currents of rabbit sinoatrial node cells","volume":"118","author":"Bois","year":"1996","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib134","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.phrs.2006.03.016","article-title":"The discovery of the selective If current inhibitor ivabradine: a new therapeutic approach to ischemic heart disease","volume":"53","author":"Vilaine","year":"2006","journal-title":"Pharmacol Res"},{"key":"10.1016\/j.ijcard.2008.12.196_bib135","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.coph.2006.09.005","article-title":"Heart rate reduction via selective \u2018funny\u2019 channel blockers","volume":"7","author":"Bucchi","year":"2007","journal-title":"Curr Opin Pharmacol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib136","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1097\/MJT.0b013e3181758855","article-title":"Characterization of the heart rate-lowering action of ivabradine, a selective If current inhibitor","volume":"15","author":"Borer","year":"2008","journal-title":"Am J Ther"},{"key":"10.1016\/j.ijcard.2008.12.196_bib137","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/S0009-9236(98)90153-9","article-title":"Pharmacokinetic-pharmacodynamic modeling of the effects of ivabradine, a direct sinus node inhibitor, on heart rate in healthy volunteers","volume":"64","author":"Ragueneau","year":"1998","journal-title":"Clin Pharmacol Ther"},{"key":"10.1016\/j.ijcard.2008.12.196_bib138","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1161\/01.CIR.0000048143.25023.87","article-title":"Antianginal and antiischemic effects of ivabradine, an If inhibitor, in stable angina: a randomized, double-blind, multicentered, placebo-controlled trial","volume":"107","author":"Borer","year":"2003","journal-title":"Circulation"},{"key":"10.1016\/j.ijcard.2008.12.196_bib139","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1159\/000108387","article-title":"Long-term safety and efficacy of ivabradine in patients with chronic stable angina","volume":"108","author":"L\u00f3pez-Besc\u00f3s","year":"2007","journal-title":"Cardiology"},{"key":"10.1016\/j.ijcard.2008.12.196_bib140","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1159\/000073933","article-title":"A single intravenous dose of ivabradine, a novel If inhibitor, lowers heart rate but does not depress left ventricular function in patients with left ventricular dysfunction","volume":"100","author":"Manz","year":"2003","journal-title":"Cardiology"},{"key":"10.1016\/j.ijcard.2008.12.196_bib141","doi-asserted-by":"crossref","first-page":"83","DOI":"10.2165\/00126839-200304020-00001","article-title":"Electrophysiological effects of a single intravenous administration of ivabradine (S 16257) in adult patients with normal baseline electrophysiology","volume":"4","author":"Camm","year":"2003","journal-title":"Drugs R D"},{"key":"10.1016\/j.ijcard.2008.12.196_bib142","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1111\/j.1540-8167.2006.00736.x","article-title":"The pacemaker current: from basics to the clinics","volume":"18","author":"Barbuti","year":"2007","journal-title":"J Cardiovasc Electrophysiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib143","doi-asserted-by":"crossref","first-page":"2256","DOI":"10.1093\/eurheartj\/ehm305","article-title":"Guidelines for cardiac pacing and cardiac resynchronization therapy","volume":"28","author":"Vardas","year":"2007","journal-title":"Eur Heart J"},{"key":"10.1016\/j.ijcard.2008.12.196_bib144","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1097\/HCO.0b013e3282f30416","article-title":"Biological pacemakers as a therapy for cardiac arrhythmias","volume":"23","author":"Marb\u00e1n","year":"2008","journal-title":"Curr Opin Cardiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib145","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.cardiores.2004.05.012","article-title":"Genes, stem cells and biological pacemakers","volume":"64","author":"Rosen","year":"2004","journal-title":"Cardiovasc Res"},{"key":"10.1016\/j.ijcard.2008.12.196_bib146","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1002\/jcp.21062","article-title":"Novel approaches for gene-specific interference via manipulating actions of microRNAs: examination on the pacemaker channel genes HCN2 and HCN4","volume":"212","author":"Xiao","year":"2007","journal-title":"J Cell Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib147","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1038\/nrg1379","article-title":"MicroRNAs: small RNAs with a big role in gene regulation","volume":"5","author":"He","year":"2004","journal-title":"Nat Rev Genet"},{"key":"10.1016\/j.ijcard.2008.12.196_bib148","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1093\/cvr\/cvn181","article-title":"Control of cardiac excitability by microRNAs","volume":"79","author":"Yang","year":"2008","journal-title":"Cardiovasc Res"},{"key":"10.1016\/j.ijcard.2008.12.196_bib149","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.coph.2007.12.013","article-title":"Implication of microRNAs in the cardiovascular system","volume":"8","author":"Scalbert","year":"2008","journal-title":"Curr Opin Pharmacol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib150","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1152\/physiolgenomics.00206.2007","article-title":"MicroRNAs put their signatures on the heart","volume":"31","author":"van Rooij","year":"2007","journal-title":"Physiol Genomics"},{"key":"10.1016\/j.ijcard.2008.12.196_bib151","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1161\/01.CIR.0000059939.97249.2C","article-title":"Expression and function of a biological pacemaker in canine heart","volume":"107","author":"Qu","year":"2003","journal-title":"Circulation"},{"key":"10.1016\/j.ijcard.2008.12.196_bib152","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1161\/01.CIR.0000114527.10764.CC","article-title":"Biological pacemaker implanted in canine left bundle branch provides ventricular escape rhythms that have physiologically acceptable rates","volume":"109","author":"Plotnikov","year":"2004","journal-title":"Circulation"},{"key":"10.1016\/j.ijcard.2008.12.196_bib153","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1161\/01.RES.0000123827.60210.72","article-title":"Human mesenchymal stem cells as a gene delivery system to create cardiac pacemakers","volume":"94","author":"Potapova","year":"2004","journal-title":"Circ Res"},{"key":"10.1016\/j.ijcard.2008.12.196_bib154","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1038\/nbt1014","article-title":"Electromechanical integration of cardiomyocytes derived from human embryonic stem cells","volume":"22","author":"Kehat","year":"2004","journal-title":"Nat Biotechnol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib155","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1161\/01.CIR.0000151313.18547.A2","article-title":"Functional integration of electrically active cardiac derivatives from genetically engineered human embryonic stem cells with quiescent recipient ventricular cardiomyocytes: insights into the development of cell-based pacemakers","volume":"111","author":"Xue","year":"2005","journal-title":"Circulation"},{"key":"10.1016\/j.ijcard.2008.12.196_bib156","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1113\/jphysiol.2003.040501","article-title":"The electrophysiological properties of spontaneously beating pacemaker cells isolated from mouse sinoatrial node","volume":"550","author":"Cho","year":"2003","journal-title":"J Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib157","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1161\/01.CIR.94.4.734","article-title":"Modulation of the hyperpolarization-activated current (If) by adenosine in rabbit sinoatrial myocytes","volume":"94","author":"Zaza","year":"1996","journal-title":"Circulation"},{"key":"10.1016\/j.ijcard.2008.12.196_bib158","first-page":"803","article-title":"Activation of the hyperpolarization-activated current (if) in sino-atrial node myocytes of the rabbit by vasoactive intestinal peptide","volume":"431","author":"Accili","year":"1996","journal-title":"Pfl\u00fcgers Arch"},{"key":"10.1016\/j.ijcard.2008.12.196_bib159","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1113\/jphysiol.1992.sp019242","article-title":"Properties of the pacemaker current (If) in latent pacemaker cells isolated from cat right atrium","volume":"453","author":"Zhou","year":"1992","journal-title":"J Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib160","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1038\/sj.bjp.0702903","article-title":"Inhibition by genistein of the hyperpolarization-activated cation current in porcine sino-atrial node cells","volume":"128","author":"Shibata","year":"1999","journal-title":"Br J Pharmacol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib161","doi-asserted-by":"crossref","first-page":"27056","DOI":"10.1074\/jbc.M502696200","article-title":"The murine HCN3 gene encodes a hyperpolarization-activated cation channel with slow kinetics and unique response to cyclic nucleotides","volume":"280","author":"Mistrik","year":"2005","journal-title":"J Biol Chem"},{"key":"10.1016\/j.ijcard.2008.12.196_bib162","doi-asserted-by":"crossref","first-page":"34635","DOI":"10.1074\/jbc.M502508200","article-title":"Functional expression of the human HCN3 channel","volume":"280","author":"Stieber","year":"2005","journal-title":"J Biol Chem"},{"key":"10.1016\/j.ijcard.2008.12.196_bib163","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1161\/CIRCULATIONAHA.106.667675","article-title":"Direct inhibition of cardiac hyperpolarization-activated cyclic nucleotide-gated pacemaker channels by clonidine","volume":"115","author":"Knaus","year":"2007","journal-title":"Circulation"},{"key":"10.1016\/j.ijcard.2008.12.196_bib164","doi-asserted-by":"crossref","first-page":"2323","DOI":"10.1093\/emboj\/18.9.2323","article-title":"Two pacemaker channels from human heart with profoundly different activation kinetics","volume":"18","author":"Ludwig","year":"1999","journal-title":"EMBO J"},{"key":"10.1016\/j.ijcard.2008.12.196_bib165","doi-asserted-by":"crossref","first-page":"29233","DOI":"10.1074\/jbc.M100830200","article-title":"Hyperpolarization-activated cyclic nucleotide-gated channel 1 is a molecular determinant of the cardiac pacemaker current If","volume":"276","author":"Moroni","year":"2001","journal-title":"J Biol Chem"},{"key":"10.1016\/j.ijcard.2008.12.196_bib166","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1111\/j.1469-7793.2000.t01-2-00593.x","article-title":"The sustained inward current and inward rectifier K+ current in pacemaker cells dissociated from rat sinoatrial node","volume":"523","author":"Shinagawa","year":"2000","journal-title":"J Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib167","first-page":"H1064","article-title":"Contribution of L-type Ca2+ current to electrical activity in sinoatrial nodal myocytes of rabbits","volume":"276","author":"Verheijck","year":"1999","journal-title":"Am J Physiol"},{"key":"10.1016\/j.ijcard.2008.12.196_bib168","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.ijcard.2008.11.048","article-title":"Ethical authorship and publishing","volume":"131","author":"Coats","year":"2009","journal-title":"Int J Cardiol"}],"container-title":["International Journal of Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0167527308015416?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0167527308015416?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T20:22:52Z","timestamp":1759090972000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0167527308015416"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,3]]},"references-count":168,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2009,3]]}},"alternative-id":["S0167527308015416"],"URL":"https:\/\/doi.org\/10.1016\/j.ijcard.2008.12.196","relation":{},"ISSN":["0167-5273"],"issn-type":[{"value":"0167-5273","type":"print"}],"subject":[],"published":{"date-parts":[[2009,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Pacemaker activity of the human sinoatrial node: Role of the hyperpolarization-activated current, If","name":"articletitle","label":"Article Title"},{"value":"International Journal of Cardiology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ijcard.2008.12.196","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2008 Elsevier Ireland Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}