{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T08:51:30Z","timestamp":1781427090065,"version":"3.54.1"},"reference-count":95,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T00:00:00Z","timestamp":1653350400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021856","name":"Ministero Dell'Universit\u00e0 e Della Ricerca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005010","name":"Associazione Italiana per La Ricerca Sul Cancro","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>BK (KCa 1.1, Slo-1) is a K<jats:sup>+<\/jats:sup> channel characterized by an allosteric regulation of the gating mechanism by Ca<jats:sup>2+<\/jats:sup> binding and voltage, and a high unitary conductance. The channel is expressed in many different tissues, where it is involved in the regulation or the fine-tuning of many physiological processes. Among other organs, BK is expressed in the pancreatic duct, a part of the gland important for the correct ionic composition of the pancreatic juice. Unfortunately, the pancreatic duct is also the site where one of the deadliest cancer types, the pancreatic duct adenocarcinoma (PDAC), develops. In the past years, it has been reported that continuous exposure of cancer cells to BK openers can have a significant impact on cell viability as well as on the ability to proliferate and migrate. Here, we first summarize the main BK channel properties and its roles in pancreatic duct physiology. Then we focus on the potential role of BK as a pharmacological target in PDAC. Moreover, we discuss how results obtained when employing BK activators on cancer cells can, in some cases, be misleading.<\/jats:p>","DOI":"10.3389\/fphar.2022.906608","type":"journal-article","created":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T06:48:37Z","timestamp":1653374917000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["BK Channel in the Physiology and in the Cancer of Pancreatic Duct: Impact and Reliability of BK Openers"],"prefix":"10.3389","volume":"13","author":[{"given":"Paolo","family":"Zuccolini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Gavazzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Pusch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1661","DOI":"10.3389\/fphys.2018.01661","article-title":"Emerging Roles of the Membrane Potential: Action beyond the Action Potential","volume":"9","author":"Abdul kadir","year":"2018","journal-title":"Front. Physiol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/0896-6273(92)90160-f","article-title":"Calcium-activated Potassium Channels Expressed from Cloned Complementary DNAs","volume":"9","author":"Adelman","year":"1992","journal-title":"Neuron"},{"key":"B3","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/s0014-5793(97)01096-x","article-title":"Stable Expression of the Human Large-Conductance Ca2+-Activated K+ Channel Alpha- and Beta-Subunits in HEK293 Cells","volume":"415","author":"Ahring","year":"1997","journal-title":"FEBS Lett."},{"key":"B4","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1124\/mol.111.075234","article-title":"The LRRC26 Protein Selectively Alters the Efficacy of BK Channel Activators","volume":"81","author":"Almassy","year":"2012","journal-title":"Mol. Pharmacol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1126\/science.1857984","article-title":"A Component of Calcium-Activated Potassium Channels Encoded by the Drosophila Slo Locus","volume":"253","author":"Atkinson","year":"1991","journal-title":"Science"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1124\/mol.107.038331","article-title":"The Small Molecule NS11021 Is a Potent and Specific Activator of Ca2+-Activated Big-Conductance K+ Channels","volume":"72","author":"Bentzen","year":"2007","journal-title":"Mol. Pharmacol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"389","DOI":"10.3389\/fphys.2014.00389","article-title":"BK Channel Activators and Their Therapeutic Perspectives","volume":"5","author":"Bentzen","year":"2014","journal-title":"Front. Physiol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1085\/jgp.84.1.1","article-title":"Ion Conductance and Selectivity of Single Calcium-Activated Potassium Channels in Cultured Rat Muscle","volume":"84","author":"Blatz","year":"1984","journal-title":"J. Gen. Physiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1007\/s00232001073","article-title":"Muscarinic Activation of BK Channels Induces Membrane Oscillations in Glioma Cells and Leads to Inhibition of Cell Migration","volume":"176","author":"Bordey","year":"2000","journal-title":"J. Membr. Biol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1038\/35038011","article-title":"Vasoregulation by the Beta1 Subunit of the Calcium-Activated Potassium Channel","volume":"407","author":"Brenner","year":"2000","journal-title":"Nature"},{"key":"B11","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1126\/science.7687074","article-title":"mSlo, a Complex Mouse Gene Encoding \"maxi\" Calcium-Activated Potassium Channels","volume":"261","author":"Butler","year":"1993","journal-title":"Science"},{"key":"B12","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1007\/s002329900379","article-title":"Single-channel Characterization of the Pharmacological Properties of the K(Ca2+) Channel of Intermediate Conductance in Bovine Aortic Endothelial Cells","volume":"163","author":"Cai","year":"1998","journal-title":"J. Membr. Biol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1097\/00006676-199510000-00008","article-title":"Regulation of Cyclic AMP Levels in guinea Pig Pancreatic Ducts and Cultured Duct Epithelial Monolayers","volume":"11","author":"De ondarza","year":"1995","journal-title":"Pancreas"},{"key":"B14","doi-asserted-by":"publisher","first-page":"E646","DOI":"10.1152\/ajpendo.00342.2018","article-title":"Glucose-mediated Inhibition of Calcium-Activated Potassium Channels Limits \u03b1-cell Calcium Influx and Glucagon Secretion","volume":"316","author":"Dickerson","year":"2019","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"B15","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1111\/apa.1989.78.s363.41","article-title":"The Pathophysiology of the Pancreatic Defect in Cystic Fibrosis","volume":"363","author":"Durie","year":"1989","journal-title":"Acta Paediatr. Scand. Suppl."},{"key":"B16","doi-asserted-by":"publisher","first-page":"5929","DOI":"10.1073\/pnas.0601296103","article-title":"High Expression of a Cytokeratin-Associated Protein in Many Cancers","volume":"103","author":"Egland","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B17","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s12943-020-01151-3","article-title":"Current Advances and Outlooks in Immunotherapy for Pancreatic Ductal Adenocarcinoma","volume":"19","author":"Fan","year":"2020","journal-title":"Mol. Cancer"},{"key":"B18","doi-asserted-by":"publisher","first-page":"8359","DOI":"10.3390\/ijms22168359","article-title":"TRPM2 Oxidation Activates Two Distinct Potassium Channels in Melanoma Cells through Intracellular Calcium Increase","volume":"22","author":"Ferrera","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B19","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1159\/000198449","article-title":"Effects of Gastrointestinal Hormones and Carbamylcholine on cAMP Accumulation in Isolated Pancreatic Duct Fragments from the Rat","volume":"20","author":"F\u00f6lsch","year":"1980","journal-title":"Digestion"},{"key":"B20","doi-asserted-by":"publisher","first-page":"11083","DOI":"10.1016\/s0021-9258(19)38560-6","article-title":"Purification and Characterization of a Unique, Potent, Peptidyl Probe for the High Conductance Calcium-Activated Potassium Channel from Venom of the Scorpion Buthus Tamulus","volume":"265","author":"Galvez","year":"1990","journal-title":"J. Biol. Chem."},{"key":"B21","doi-asserted-by":"publisher","first-page":"3552","DOI":"10.1073\/pnas.1114321109","article-title":"Molecular Mechanism of Pharmacological Activation of BK Channels","volume":"109","author":"Gessner","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B22","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1085\/jgp.112.4.485","article-title":"Mechanism of Maxi-K Channel Activation by Dehydrosoyasaponin-I","volume":"112","author":"Giangiacomo","year":"1998","journal-title":"J. Gen. Physiol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"157","DOI":"10.3390\/md16050157","article-title":"The Maxi-K (BK) Channel Antagonist Penitrem A as a Novel Breast Cancer-Targeted Therapeutic","volume":"16","author":"Goda","year":"2018","journal-title":"Mar. Drugs"},{"key":"B24","doi-asserted-by":"publisher","first-page":"e2107026118","DOI":"10.1073\/pnas.2107026118","article-title":"NMDA Receptor-BK Channel Coupling Regulates Synaptic Plasticity in the Barrel Cortex","volume":"118","author":"G\u00f3mez","year":"2021","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B25","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1146\/annurev-physiol-022516-034038","article-title":"Regulation of BK Channels by Beta and Gamma Subunits","volume":"81","author":"Gonzalez-perez","year":"2019","journal-title":"Annu. Rev. Physiol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1113\/JP281952","article-title":"The LRRC Family of BK Channel Regulatory Subunits: Potential Roles in Health and Disease","volume":"600","author":"Gonzalez-perez","year":"2022","journal-title":"J. Physiol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1007\/BF01868636","article-title":"Regulation of Maxi-K+ Channels on Pancreatic Duct Cells by Cyclic AMP-dependent Phosphorylation","volume":"115","author":"Gray","year":"1990","journal-title":"J. Membr. Biol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"109","DOI":"10.5483\/bmbrep.2017.50.3.033","article-title":"Calcium-activated Chloride Channels: a New Target to Control the Spiking Pattern of Neurons","volume":"50","author":"Ha","year":"2017","journal-title":"BMB Rep."},{"key":"B29","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.bbrc.2008.07.161","article-title":"The Potassium Ion Channel Opener NS1619 Inhibits Proliferation and Induces Apoptosis in A2780 Ovarian Cancer Cells","volume":"375","author":"Han","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B30","doi-asserted-by":"publisher","first-page":"432","DOI":"10.4161\/chan.26100","article-title":"Molecular Basis of Potassium Channels in Pancreatic Duct Epithelial Cells","volume":"7","author":"Hayashi","year":"2013","journal-title":"Channels (Austin)"},{"key":"B31","doi-asserted-by":"publisher","first-page":"C151","DOI":"10.1152\/ajpcell.00089.2012","article-title":"An Intermediate-Conductance Ca2+-Activated K+ Channel Is Important for Secretion in Pancreatic Duct Cells","volume":"303","author":"Hayashi","year":"2012","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"31784","DOI":"10.1074\/jbc.274.45.31784","article-title":"Purinoceptors Evoke Different Electrophysiological Responses in Pancreatic Ducts. P2Y Inhibits K(+) Conductance, and P2X Stimulates Cation Conductance","volume":"274","author":"Hede","year":"1999","journal-title":"J. Biol. Chem."},{"key":"B33","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1007\/s00424-005-1433-3","article-title":"P2Y2 and P2Y4 Receptors Regulate Pancreatic Ca(2+)-Activated K+ Channels Differently","volume":"450","author":"Hede","year":"2005","journal-title":"Pflugers Arch."},{"key":"B34","doi-asserted-by":"publisher","first-page":"R60","DOI":"10.1152\/ajpregu.2000.279.1.R60","article-title":"Regulation of Urinary Bladder Smooth Muscle Contractions by Ryanodine Receptors and BK and SK Channels","volume":"279","author":"Herrera","year":"2000","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1038\/nature20775","article-title":"Structural Basis for Gating the High-Conductance Ca2+-Activated K+ Channel","volume":"541","author":"Hite","year":"2017","journal-title":"Nature"},{"key":"B36","first-page":"188","article-title":"Small Cell Lung Cancer Cells Express the Late Stage gBK Tumor Antigen: a Possible Immunotarget for the Terminal Disease","volume":"6","author":"Hoa","year":"2014","journal-title":"Am. J. Transl. Res."},{"key":"B37","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1038\/labinvest.3700506","article-title":"Human Monocytes Kill M-CSF-Expressing Glioma Cells by BK Channel Activation","volume":"87","author":"Hoa","year":"2007","journal-title":"Lab. Invest."},{"key":"B38","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1085\/jgp.20028605","article-title":"Coupling between Voltage Sensor Activation, Ca2+ Binding and Channel Opening in Large Conductance (BK) Potassium Channels","volume":"120","author":"Horrigan","year":"2002","journal-title":"J. Gen. Physiol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1124\/mol.62.4.836","article-title":"Molecular Basis of Pimarane Compounds as Novel Activators of Large-Conductance Ca(2+)-Activated K(+) Channel Alpha-Subunit","volume":"62","author":"Imaizumi","year":"2002","journal-title":"Mol. Pharmacol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1111\/j.1469-7793.1999.0551m.x","article-title":"Luminal ATP Stimulates Fluid and HCO3- Secretion in guinea-pig Pancreatic Duct","author":"Ishiguro","year":"1999","journal-title":"J. Physiol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"3525","DOI":"10.1113\/jphysiol.2010.190207","article-title":"Calcium-activated and Voltage-Gated Potassium Channels of the Pancreatic Islet Impart Distinct and Complementary Roles during Secretagogue Induced Electrical Responses","volume":"588","author":"Jacobson","year":"2010","journal-title":"J. Physiol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1038\/nbt.3080","article-title":"A Comprehensive Transcriptional Portrait of Human Cancer Cell Lines","volume":"33","author":"Klijn","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"5819","DOI":"10.1021\/bi00185a021","article-title":"Tremorgenic Indole Alkaloids Potently Inhibit Smooth Muscle High-Conductance Calcium-Activated Potassium Channels","volume":"33","author":"Knaus","year":"1994","journal-title":"Biochemistry"},{"key":"B44","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/0304-3940(94)90736-6","article-title":"Activating Effect of the Flavonoid Phloretin on Ca(2+)-Activated K+ Channels in Myelinated Nerve Fibers of Xenopus laevis [corrected]","volume":"165","author":"Koh","year":"1994","journal-title":"Neurosci. Lett."},{"key":"B45","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1007\/s00424-003-1012-4","article-title":"BK Channel Openers Inhibit Migration of Human Glioma Cells","volume":"446","author":"Kraft","year":"2003","journal-title":"Pflugers Arch."},{"key":"B46","doi-asserted-by":"publisher","first-page":"258","DOI":"10.3389\/fnmol.2018.00258","article-title":"Physiological Roles and Therapeutic Potential of Ca2+ Activated Potassium Channels in the Nervous System","volume":"11","author":"Kshatri","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"B47","doi-asserted-by":"publisher","first-page":"2685","DOI":"10.1016\/j.bbamem.2014.12.016","article-title":"Ion Channel Expression as Promising Cancer Biomarker","volume":"1848","author":"Lastraioli","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"B48","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1152\/physrev.00001.2016","article-title":"Molecular Determinants of BK Channel Functional Diversity and Functioning","volume":"97","author":"Latorre","year":"2017","journal-title":"Physiol. Rev."},{"key":"B49","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1152\/physrev.00011.2011","article-title":"Molecular Mechanism of Pancreatic and Salivary Gland Fluid and HCO3 Secretion","volume":"92","author":"Lee","year":"2012","journal-title":"Physiol. Rev."},{"key":"B50","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.gene.2018.02.055","article-title":"The Role of BKCa in Endometrial Cancer HEC-1-B Cell Proliferation and Migration","volume":"655","author":"Li","year":"2018","journal-title":"Gene"},{"key":"B51","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/bs.irn.2016.03.015","article-title":"Modulation of BK Channel Function by Auxiliary Beta and Gamma Subunits","volume":"128","author":"Li","year":"2016","journal-title":"Int. Rev. Neurobiol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1840","DOI":"10.1523\/jneurosci.22-05-01840.2002","article-title":"Cloning and Characterization of Glioma BK, a Novel BK Channel Isoform Highly Expressed in Human Glioma Cells","volume":"22","author":"Liu","year":"2002","journal-title":"J. Neurosci."},{"key":"B53","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1007\/s00424-012-1214-8","article-title":"Single-channel Biophysical and Pharmacological Characterizations of Native Human Large-Conductance Calcium-Activated Potassium Channels in Freshly Isolated Detrusor Smooth Muscle Cells","volume":"465","author":"Malysz","year":"2013","journal-title":"Pflugers Arch."},{"key":"B54","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1038\/291497a0","article-title":"Ca-dependent K Channels with Large Unitary Conductance in Chromaffin Cell Membranes","volume":"291","author":"Marty","year":"1981","journal-title":"Nature"},{"key":"B55","doi-asserted-by":"publisher","first-page":"6128","DOI":"10.1021\/bi00075a002","article-title":"An Activator of Calcium-dependent Potassium Channels Isolated from a Medicinal Herb","volume":"32","author":"Mcmanus","year":"1993","journal-title":"Biochemistry"},{"key":"B56","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1016\/0896-6273(95)90321-6","article-title":"Functional Role of the Beta Subunit of High Conductance Calcium-Activated Potassium Channels","volume":"14","author":"Mcmanus","year":"1995","journal-title":"Neuron"},{"key":"B57","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1016\/0300-9629(72)90128-4","article-title":"Intracellular Calcium Injection Causes Increased Potassium Conductance in Aplysia Nerve Cells","volume":"42","author":"Meech","year":"1972","journal-title":"Comp. Biochem. Physiol. A Comp. Physiol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"43P","DOI":"10.1113\/jphysiol.1974.sp010481","article-title":"Calcium-mediated Potassium Activation in Helix Neurones","volume":"237","author":"Meech","year":"1974","journal-title":"J. Physiol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1038\/313316a0","article-title":"Charybdotoxin, a Protein Inhibitor of Single Ca2+-Activated K+ Channels from Mammalian Skeletal Muscle","volume":"313","author":"Miller","year":"1985","journal-title":"Nature"},{"key":"B60","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1124\/jpet.113.212662","article-title":"NS19504: a Novel BK Channel Activator with Relaxing Effect on Bladder Smooth Muscle Spontaneous Phasic Contractions","volume":"350","author":"Nausch","year":"2014","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1032","DOI":"10.1016\/j.bbrc.2020.02.176","article-title":"Involvement of the \u03b31 Subunit of the Large-Conductance Ca2+-Activated K+ Channel in the Proliferation of Human Somatostatinoma Cells","volume":"525","author":"Noda","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B62","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/0014-2999(94)90442-1","article-title":"Selective Activation of Ca(2+)-dependent K+ Channels by Novel Benzimidazolone","volume":"251","author":"Olesen","year":"1994","journal-title":"Eur. J. Pharmacol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1038\/293471a0","article-title":"Single Channel Recordings of Ca2+-Activated K+ Currents in Rat Muscle Cell Culture","volume":"293","author":"Pallotta","year":"1981","journal-title":"Nature"},{"key":"B64","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.bbrc.2007.07.057","article-title":"The Mitochondrial Ca2+-Activated K+ Channel Activator, NS 1619 Inhibits L-type Ca2+ Channels in Rat Ventricular Myocytes","volume":"362","author":"Park","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B65","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1152\/jn.2001.85.2.790","article-title":"BK Channels in Human Glioma Cells","volume":"85","author":"Ransom","year":"2001","journal-title":"J. Neurophysiol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"25","DOI":"10.3390\/antiox9010025","article-title":"Natural Antioxidants Beneficial Effects on Anion Exchange through Band 3 Protein in Human Erythrocytes","volume":"9","author":"Remigante","year":"2019","journal-title":"Antioxidants (Basel)"},{"key":"B67","doi-asserted-by":"publisher","first-page":"6144","DOI":"10.3390\/cancers13236144","article-title":"NS-11021 Modulates Cancer-Associated Processes Independently of BK Channels in Melanoma and Pancreatic Duct Adenocarcinoma Cell Lines","volume":"13","author":"Remigante","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B68","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1038\/sj.ki.5002369","article-title":"The Role of the BK Channel in Potassium Homeostasis and Flow-Induced Renal Potassium Excretion","volume":"72","author":"Rieg","year":"2007","journal-title":"Kidney Int."},{"key":"B69","doi-asserted-by":"publisher","first-page":"e201912506","DOI":"10.1085\/jgp.201912506","article-title":"Molecular Mechanism of BK Channel Activation by the Smooth Muscle Relaxant NS11021","volume":"152","author":"Rockman","year":"2020","journal-title":"J. Gen. Physiol."},{"key":"B70","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1021\/jm061006n","article-title":"3-[(5-Chloro-2-hydroxyphenyl)methyl]-5-[4-(trifluoromethyl)phenyl ]-1,3,4-Oxadiazol-2(3h)-One, BMS-191011: Opener of Large-Conductance Ca(2+)-Activated Potassium (Maxi-K) Channels, Identification, Solubility, and SAR","volume":"50","author":"Romine","year":"2007","journal-title":"J. Med. Chem."},{"key":"B71","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.1124\/jpet.106.118786","article-title":"Stimulation of Ca2+-Gated Cl- Currents by the Calcium-dependent K+ Channel Modulators NS1619 [1,3-Dihydro-1-[2-Hydroxy-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2h-Benzimidazol-2-One] and Isopimaric Acid","volume":"321","author":"Saleh","year":"2007","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"B72","doi-asserted-by":"publisher","first-page":"750615","DOI":"10.3389\/fphys.2021.750615","article-title":"The Large-Conductance, Calcium-Activated Potassium Channel: A Big Key Regulator of Cell Physiology","volume":"12","author":"Sancho","year":"2021","journal-title":"Front. Physiol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1002\/path.2159","article-title":"Altered Cryptal Expression of Luminal Potassium (BK) Channels in Ulcerative Colitis","volume":"212","author":"Sandle","year":"2007","journal-title":"J. Pathol."},{"key":"B74","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/00006676-199601000-00001","article-title":"Pancreatic Dysfunction in Cystic Fibrosis Occurs as a Result of Impairments in Luminal pH, Apical Trafficking of Zymogen Granule Membranes, and Solubilization of Secretory Enzymes","volume":"12","author":"Scheele","year":"1996","journal-title":"Pancreas"},{"key":"B75","doi-asserted-by":"publisher","first-page":"568993","DOI":"10.3389\/fphar.2020.568993","article-title":"Ion Channel Signature in Healthy Pancreas and Pancreatic Ductal Adenocarcinoma","volume":"11","author":"Schnipper","year":"2020","journal-title":"Front. Pharmacol."},{"key":"B76","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1038\/nature00941","article-title":"Mechanism of Magnesium Activation of Calcium-Activated Potassium Channels","volume":"418","author":"Shi","year":"2002","journal-title":"Nature"},{"key":"B77","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1186\/s12885-020-07071-1","article-title":"Opening Large-Conductance Potassium Channels Selectively Induced Cell Death of Triple-Negative Breast Cancer","volume":"20","author":"Sizemore","year":"2020","journal-title":"BMC Cancer"},{"key":"B78","doi-asserted-by":"publisher","first-page":"G1307","DOI":"10.1152\/ajpgi.90697.2008","article-title":"Functional Coupling of Apical Cl-\/HCO3- Exchange with CFTR in Stimulated HCO3- Secretion by guinea Pig Interlobular Pancreatic Duct","volume":"296","author":"Stewart","year":"2009","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"B79","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1038\/nature20608","article-title":"Cryo-EM Structure of the Open High-Conductance Ca2+-Activated K+ Channel","volume":"541","author":"Tao","year":"2017","journal-title":"Nature"},{"key":"B80","doi-asserted-by":"publisher","first-page":"e51409","DOI":"10.7554\/eLife.51409","article-title":"Molecular Structures of the Human Slo1 K+ Channel in Complex with \u03b24","volume":"8","author":"Tao","year":"2019","journal-title":"Elife"},{"key":"B81","doi-asserted-by":"publisher","first-page":"7717","DOI":"10.1074\/jbc.C000741200","article-title":"Alternative Splicing Switches Potassium Channel Sensitivity to Protein Phosphorylation","volume":"276","author":"Tian","year":"2001","journal-title":"J. Biol. Chem."},{"key":"B82","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1136\/gut.2010.214213","article-title":"Pathophysiological Relevance of Apical Large-Conductance Ca\u00b2+-Activated Potassium Channels in Pancreatic Duct Epithelial Cells","volume":"60","author":"Venglovecz","year":"2011","journal-title":"Gut"},{"key":"B83","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1007\/s00424-014-1585-0","article-title":"Potassium Channels in Pancreatic Duct Epithelial Cells: Their Role, Function and Pathophysiological Relevance","volume":"467","author":"Venglovecz","year":"2015","journal-title":"Pflugers Arch."},{"key":"B84","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1136\/gut.2007.134361","article-title":"Effects of Bile Acids on Pancreatic Ductal Bicarbonate Secretion in guinea Pig","volume":"57","author":"Venglovecz","year":"2008","journal-title":"Gut"},{"key":"B85","volume-title":"Ion Channels in Pancreatic Duct Epithelial Cells in Health and Disease","author":"Venglovecz","year":"2021"},{"key":"B86","doi-asserted-by":"publisher","first-page":"5049","DOI":"10.1038\/sj.emboj.7601387","article-title":"Slc26a6 Regulates CFTR Activity In Vivo to Determine Pancreatic Duct HCO3- Secretion: Relevance to Cystic Fibrosis","volume":"25","author":"Wang","year":"2006","journal-title":"EMBO J."},{"key":"B87","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.ceca.2014.03.005","article-title":"The Potassium Channel Opener NS1619 Modulates Calcium Homeostasis in Muscle Cells by Inhibiting SERCA","volume":"56","author":"Wrzosek","year":"2014","journal-title":"Cell Calcium"},{"key":"B88","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1002\/jcp.20866","article-title":"Potent Stimulation of Large-Conductance Ca2+-Activated K+ Channels by Rottlerin, an Inhibitor of Protein Kinase C-Delta, in Pituitary Tumor (GH3) Cells and in Cortical Neuronal (HCN-1A) Cells","volume":"210","author":"Wu","year":"2007","journal-title":"J. Cell Physiol."},{"key":"B89","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1038\/nature00956","article-title":"Multiple Regulatory Sites in Large-Conductance Calcium-Activated Potassium Channels","volume":"418","author":"Xia","year":"2002","journal-title":"Nature"},{"key":"B90","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1038\/sj.bjp.0703885","article-title":"BK Channel Activation by NS-1619 Is Partially Mediated by Intracellular Ca2+ Release in Smooth Muscle Cells of Porcine Coronary Artery","volume":"132","author":"Yamamura","year":"2001","journal-title":"Br. J. Pharmacol."},{"key":"B91","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1038\/nsmb.1507","article-title":"Activation of Slo1 BK Channels by Mg2+ Coordinated between the Voltage Sensor and RCK1 Domains","volume":"15","author":"Yang","year":"2008","journal-title":"Nat. Struct. Mol. Biol."},{"key":"B92","doi-asserted-by":"publisher","first-page":"30882","DOI":"10.1074\/jbc.M505302200","article-title":"Activation of the BK (SLO1) Potassium Channel by Mallotoxin","volume":"280","author":"Zakharov","year":"2005","journal-title":"J. Biol. Chem."},{"key":"B93","doi-asserted-by":"publisher","first-page":"E9006","DOI":"10.1073\/pnas.1802567115","article-title":"Glutamate-activated BK Channel Complexes Formed with NMDA Receptors","volume":"115","author":"Zhang","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B94","doi-asserted-by":"publisher","first-page":"604531","DOI":"10.3389\/fonc.2020.604531","article-title":"Research Progress of Pancreas-Related Microorganisms and Pancreatic Cancer","volume":"10","author":"Zhang","year":"2020","journal-title":"Front. Oncol."},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15810","article-title":"The VRAC Blocker DCPIB Directly Gates the BK Channels and Increases Intracellular Ca2+ in Melanoma and Pancreatic Duct Adenocarcinoma Cell Lines","author":"Zuccolini","year":"2022","journal-title":"Br. J. Pharmacol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.906608\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T06:48:43Z","timestamp":1653374923000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.906608\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,24]]},"references-count":95,"alternative-id":["10.3389\/fphar.2022.906608"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2022.906608","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,24]]},"article-number":"906608"}}