{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:17:35Z","timestamp":1790749055340,"version":"4.1.0"},"reference-count":89,"publisher":"Rockefeller University Press","issue":"5","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,11,1]]},"abstract":"<jats:p>Modulation of L-type Ca2+ current (ICa,L) by H+ ions in cardiac myocytes is controversial, with widely discrepant responses reported. The pH sensitivity of ICa,L was investigated (whole cell voltage clamp) while measuring intracellular Ca2+ (Ca2+i) or pHi (epifluorescence microscopy) in rabbit and guinea pig ventricular myocytes. Selectively reducing extracellular or intracellular pH (pHo 6.5 and pHi 6.7) had opposite effects on ICa,L gating, shifting the steady-state activation and inactivation curves to the right and left, respectively, along the voltage axis. At low pHo, this decreased ICa,L, whereas at low pHi, it increased ICa,L at clamp potentials negative to 0 mV, although the current decreased at more positive potentials. When Ca2+i was buffered with BAPTA, the stimulatory effect of low pHi was even more marked, with essentially no inhibition. We conclude that extracellular H+ ions inhibit whereas intracellular H+ ions can stimulate ICa,L. Low pHi and pHo effects on ICa,L were additive, tending to cancel when appropriately combined. They persisted after inhibition of calmodulin kinase II (with KN-93). Effects are consistent with H+ ion screening of fixed negative charge at the sarcolemma, with additional channel block by H+o and Ca2+i. Action potential duration (APD) was also strongly H+ sensitive, being shortened by low pHo, but lengthened by low pHi, caused mainly by H+-induced changes in late Ca2+ entry through the L-type Ca2+ channel. Kinetic analyses of pH-sensitive channel gating, when combined with whole cell modeling, successfully predicted the APD changes, plus many of the accompanying changes in Ca2+ signaling. We conclude that the pHi-versus-pHo control of ICa,L will exert a major influence on electrical and Ca2+-dependent signaling during acid\u2013base disturbances in the heart.<\/jats:p>","DOI":"10.1085\/jgp.201110658","type":"journal-article","created":{"date-parts":[[2011,10,31]],"date-time":"2011-10-31T11:54:01Z","timestamp":1320062041000},"page":"537-559","update-policy":"https:\/\/doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":48,"title":["Influence of pH on Ca2+ current and its control of electrical and Ca2+ signaling in ventricular myocytes"],"prefix":"10.1085","volume":"138","author":[{"given":"Noriko","family":"Saegusa","sequence":"first","affiliation":[{"name":"Department of Physiology, Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT 84112 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Moorhouse","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Genetics, Burdon Sanderson Cardiac Science Centre, Oxford University, Oxford OX1 3PT, England, UK 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard D.","family":"Vaughan-Jones","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Genetics, Burdon Sanderson Cardiac Science Centre, Oxford University, Oxford OX1 3PT, England, UK 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth W.","family":"Spitzer","sequence":"additional","affiliation":[{"name":"Department of Physiology, Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, UT 84112 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2011,10,31]]},"reference":[{"key":"2023072521371768800_bib1","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1085\/jgp.108.5.435","article-title":"Cross-signaling between L-type Ca2+ channels and ryanodine receptors in rat ventricular myocytes","volume":"108","author":"Adachi-Akahane","year":"1996","journal-title":"J. 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Physiol."},{"key":"2023072521371768800_bib41","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1016\/S0008-6363(96)00217-9","article-title":"Ca2+- and caffeine-induced Ca2+ release from the sarcoplasmic reticulum in rat skinned trabeculae: effects of pH and Pi","volume":"33","author":"Kentish","year":"1997","journal-title":"Cardiovasc. 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J."},{"key":"2023072521371768800_bib51","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.abb.2005.02.025","article-title":"Ca2+- and voltage-dependent inactivation of the expressed L-type Ca(v)1.2 calcium channel","volume":"437","author":"Lacinov\u00e1","year":"2005","journal-title":"Arch. Biochem. Biophys."},{"key":"2023072521371768800_bib52","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1113\/jphysiol.1985.sp015752","article-title":"Inactivation of calcium channels in mammalian heart cells: joint dependence on membrane potential and intracellular calcium","volume":"364","author":"Lee","year":"1985","journal-title":"J. Physiol."},{"key":"2023072521371768800_bib53","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1111\/j.1469-7793.1998.425bb.x","article-title":"Control of L-type calcium current during the action potential of guinea-pig ventricular myocytes","volume":"513","author":"Linz","year":"1998","journal-title":"J. Physiol."},{"key":"2023072521371768800_bib54","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1007\/s004240050982","article-title":"Profile and kinetics of L-type calcium current during the cardiac ventricular action potential compared in guinea-pigs, rats and rabbits","volume":"439","author":"Linz","year":"2000","journal-title":"Pflugers Arch."},{"key":"2023072521371768800_bib55","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1161\/01.RES.74.6.1071","article-title":"A dynamic model of the cardiac ventricular action potential. I. Simulations of ionic currents and concentration changes","volume":"74","author":"Luo","year":"1994","journal-title":"Circ. Res."},{"key":"2023072521371768800_bib56","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1529\/biophysj.106.98160","article-title":"A rabbit ventricular action potential model replicating cardiac dynamics at rapid heart rates","volume":"94","author":"Mahajan","year":"2008","journal-title":"Biophys. 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Physiol."},{"key":"2023072521371768800_bib63","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1016\/0005-2736(88)90557-3","article-title":"Phospholipid asymmetry in cardiac sarcolemma. Analysis of intact cells and \u2018gas-dissected\u2019 membranes","volume":"943","author":"Post","year":"1988","journal-title":"Biochim. Biophys. Acta."},{"key":"2023072521371768800_bib64","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1007\/s004240050296","article-title":"Two-sided action of protons on an inward rectifier K+ channel (IRK1)","volume":"433","author":"Sabirov","year":"1997","journal-title":"Pflugers Arch."},{"key":"2023072521371768800_bib65","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1113\/jphysiol.2002.026468","article-title":"Regulation of cardiac excitation-contraction coupling by action potential repolarization: role of the transient outward potassium current (Ito)","volume":"546","author":"Sah","year":"2003","journal-title":"J. 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Physiol."},{"key":"2023072521371768800_bib72","doi-asserted-by":"crossref","first-page":"C316","DOI":"10.1152\/ajpcell.1992.262.2.C316","article-title":"Relationship between intracellular pH and tension development in resting ventricular muscle and myocytes","volume":"262","author":"Spitzer","year":"1992","journal-title":"Am. J. Physiol."},{"key":"2023072521371768800_bib73","first-page":"H1625","article-title":"Mechanisms of inactivation of L-type calcium channels in human atrial myocytes","volume":"272","author":"Sun","year":"1997","journal-title":"Am. J. Physiol."},{"key":"2023072521371768800_bib74","doi-asserted-by":"crossref","first-page":"3P","DOI":"10.1113\/jphysiol.1984.sp015397","article-title":"Experimental displacement of intracellular pH and the mechanism of its subsequent recovery","volume":"354","author":"Thomas","year":"1984","journal-title":"J. Physiol."},{"key":"2023072521371768800_bib75","first-page":"H364","article-title":"Different effects of intracellular Ca and protein kinase C on cardiac T and L Ca currents","volume":"261","author":"Tseng","year":"1991","journal-title":"Am. J. Physiol."},{"key":"2023072521371768800_bib76","doi-asserted-by":"publisher","first-page":"2396","DOI":"10.1021\/bi00552a018","article-title":"New calcium indicators and buffers with high selectivity against magnesium and protons: design, synthesis, and properties of prototype structures","volume":"19","author":"Tsien","year":"1980","journal-title":"Biochemistry."},{"key":"2023072521371768800_bib77","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1113\/jphysiol.2001.013267","article-title":"Intrinsic H(+) ion mobility in the rabbit ventricular myocyte","volume":"541","author":"Vaughan-Jones","year":"2002","journal-title":"J. Physiol."},{"key":"2023072521371768800_bib78","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1016\/j.yjmcc.2008.10.024","article-title":"Intracellular pH regulation in heart","volume":"46","author":"Vaughan-Jones","year":"2009","journal-title":"J. Mol. Cell. Cardiol."},{"key":"2023072521371768800_bib79","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1007\/s004240051000","article-title":"The effect of external pH on the delayed rectifying K+ current in cardiac ventricular myocytes","volume":"439","author":"Vereecke","year":"2000","journal-title":"Pflugers Arch."},{"key":"2023072521371768800_bib80","first-page":"H2168","article-title":"CaM kinase augments cardiac L-type Ca2+ current: a cellular mechanism for long Q-T arrhythmias","volume":"276","author":"Wu","year":"1999","journal-title":"Am. J. Physiol."},{"key":"2023072521371768800_bib81","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1161\/01.RES.79.6.1100","article-title":"Regulation of cardiac Ca2+ release channel (ryanodine receptor) by Ca2+, H+, Mg2+, and adenine nucleotides under normal and simulated ischemic conditions","volume":"79","author":"Xu","year":"1996","journal-title":"Circ. Res."},{"key":"2023072521371768800_bib82","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1006\/jmcc.1996.0292","article-title":"Proton inhibition of transient outward potassium current in rat ventricular myocytes","volume":"29","author":"Xu","year":"1997","journal-title":"J. Mol. Cell. Cardiol."},{"key":"2023072521371768800_bib83","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1113\/jphysiol.2004.071068","article-title":"Functional diversity of electrogenic Na+-HCO3- cotransport in ventricular myocytes from rat, rabbit and guinea pig","volume":"562","author":"Yamamoto","year":"2005","journal-title":"J. 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