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. 1990 Jun 1;95(6):1077–1102. doi: 10.1085/jgp.95.6.1077

Chloride current in mammalian cardiac myocytes. Novel mechanism for autonomic regulation of action potential duration and resting membrane potential

PMCID: PMC2216356  PMID: 2165130

Abstract

The properties of the autonomically regulated chloride current (ICl) were studied in isolated guinea pig ventricular myocytes. This current was elicited upon exposure to isoproterenol (ISO) and reversed upon concurrent exposure to acetylcholine (ACh). ICl was time independent and exhibited outward rectification. The responses to ISO and ACh could be blocked by propranolol and atropine, respectively, and ICl was also elicited by forskolin, 8-bromoadenosine 3',5'-cyclic monophosphate, and 3-isobutyl-l-methylxanthine, indicating that the current is regulated through a cAMP-dependent pathway. The reversal potential of the ISO- induced current followed the predicted chloride equilibrium potential, consistent with it being carried predominantly by Cl-. Activation of ICl produced changes in the resting membrane potential and action potential duration, which were Cl- gradient dependent. These results indicate that under physiological conditions ICl may play an important role in regulating action potential duration and resting membrane potential in mammalian cardiac myocytes.

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Selected References

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  1. Bahinski A., Nairn A. C., Greengard P., Gadsby D. C. Chloride conductance regulated by cyclic AMP-dependent protein kinase in cardiac myocytes. Nature. 1989 Aug 31;340(6236):718–721. doi: 10.1038/340718a0. [DOI] [PubMed] [Google Scholar]
  2. Barish M. E. A transient calcium-dependent chloride current in the immature Xenopus oocyte. J Physiol. 1983 Sep;342:309–325. doi: 10.1113/jphysiol.1983.sp014852. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baumgarten C. M., Fozzard H. A. Intracellular chloride activity in mammalian ventricular muscle. Am J Physiol. 1981 Sep;241(3):C121–C129. doi: 10.1152/ajpcell.1981.241.3.C121. [DOI] [PubMed] [Google Scholar]
  4. Blatz A. L., Magleby K. L. Ion conductance and selectivity of single calcium-activated potassium channels in cultured rat muscle. J Gen Physiol. 1984 Jul;84(1):1–23. doi: 10.1085/jgp.84.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Blatz A. L., Magleby K. L. Quantitative description of three modes of activity of fast chloride channels from rat skeletal muscle. J Physiol. 1986 Sep;378:141–174. doi: 10.1113/jphysiol.1986.sp016212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Byrne N. G., Large W. A. Action of noradrenaline on single smooth muscle cells freshly dispersed from the rat anococcygeus muscle. J Physiol. 1987 Aug;389:513–525. doi: 10.1113/jphysiol.1987.sp016669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Byrne N. G., Large W. A. Membrane ionic mechanisms activated by noradrenaline in cells isolated from the rabbit portal vein. J Physiol. 1988 Oct;404:557–573. doi: 10.1113/jphysiol.1988.sp017306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. CARMELIET E. E. Chloride ions and the membrane potential of Purkinje fibres. J Physiol. 1961 Apr;156:375–388. doi: 10.1113/jphysiol.1961.sp006682. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Carmeliet E. Induction and removal of inward-going rectification in sheep cardiac Purkinje fibres. J Physiol. 1982 Jun;327:285–308. doi: 10.1113/jphysiol.1982.sp014232. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Coraboeuf E., Carmeliet E. Existence of two transient outward currents in sheep cardiac Purkinje fibers. Pflugers Arch. 1982 Feb;392(4):352–359. doi: 10.1007/BF00581631. [DOI] [PubMed] [Google Scholar]
  11. Coronado R., Latorre R. Detection of K+ and Cl-channels from calf cardiac sarcolemma in planar lipid bilayer membranes. Nature. 1982 Aug 26;298(5877):849–852. doi: 10.1038/298849a0. [DOI] [PubMed] [Google Scholar]
  12. Coronado R., Latorre R. Phospholipid bilayers made from monolayers on patch-clamp pipettes. Biophys J. 1983 Aug;43(2):231–236. doi: 10.1016/S0006-3495(83)84343-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. DECK K. A., KERN R., TRAUTWEIN W. VOLTAGE CLAMP TECHNIQUE IN MAMMALIAN CARDIAC FIBRES. Pflugers Arch Gesamte Physiol Menschen Tiere. 1964 Jun 9;280:50–62. doi: 10.1007/BF00412615. [DOI] [PubMed] [Google Scholar]
  14. DECK K. A., TRAUTWEIN W. IONIC CURRENTS IN CARDIAC EXCITATION. Pflugers Arch Gesamte Physiol Menschen Tiere. 1964 Jun 9;280:63–80. doi: 10.1007/BF00412616. [DOI] [PubMed] [Google Scholar]
  15. DiFrancesco D. The cardiac hyperpolarizing-activated current, if. Origins and developments. Prog Biophys Mol Biol. 1985;46(3):163–183. doi: 10.1016/0079-6107(85)90008-2. [DOI] [PubMed] [Google Scholar]
  16. Dudel J., Peper K., Rüdel R., Trautwein W. The dynamic chloride component of membrane current in Purkinje fibers. Pflugers Arch Gesamte Physiol Menschen Tiere. 1967;295(3):197–212. doi: 10.1007/BF01844100. [DOI] [PubMed] [Google Scholar]
  17. Désilets M., Baumgarten C. M. Isoproterenol directly stimulates the Na+-K+ pump in isolated cardiac myocytes. Am J Physiol. 1986 Jul;251(1 Pt 2):H218–H225. doi: 10.1152/ajpheart.1986.251.1.H218. [DOI] [PubMed] [Google Scholar]
  18. Désilets M., Baumgarten C. M. K+, Na+, and Cl- activities in ventricular myocytes isolated from rabbit heart. Am J Physiol. 1986 Aug;251(2 Pt 1):C197–C208. doi: 10.1152/ajpcell.1986.251.2.C197. [DOI] [PubMed] [Google Scholar]
  19. Egan T. M., Noble D., Noble S. J., Powell T., Twist V. W. An isoprenaline activated sodium-dependent inward current in ventricular myocytes. Nature. 1987 Aug 13;328(6131):634–637. doi: 10.1038/328634a0. [DOI] [PubMed] [Google Scholar]
  20. Egan T. M., Noble D., Noble S. J., Powell T., Twist V. W., Yamaoka K. On the mechanism of isoprenaline- and forskolin-induced depolarization of single guinea-pig ventricular myocytes. J Physiol. 1988 Jun;400:299–320. doi: 10.1113/jphysiol.1988.sp017121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Escande D., Loisance D., Planche C., Coraboeuf E. Age-related changes of action potential plateau shape in isolated human atrial fibers. Am J Physiol. 1985 Oct;249(4 Pt 2):H843–H850. doi: 10.1152/ajpheart.1985.249.4.H843. [DOI] [PubMed] [Google Scholar]
  22. Escande D., Thuringer D., Leguern S., Cavero I. The potassium channel opener cromakalim (BRL 34915) activates ATP-dependent K+ channels in isolated cardiac myocytes. Biochem Biophys Res Commun. 1988 Jul 29;154(2):620–625. doi: 10.1016/0006-291x(88)90184-2. [DOI] [PubMed] [Google Scholar]
  23. Fong C. N., Hinke J. A. Intracellular Cl activity, Cl binding, and 36Cl efflux in rabbit papillary muscle. Can J Physiol Pharmacol. 1981 May;59(5):479–484. doi: 10.1139/y81-071. [DOI] [PubMed] [Google Scholar]
  24. Fozzard H. A., Hiraoka M. The positive dynamic current and its inactivation properties in cardiac Purkinje fibres. J Physiol. 1973 Nov;234(3):569–586. doi: 10.1113/jphysiol.1973.sp010361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Gadsby D. C., Cranefield P. F. Two levels of resting potential in cardiac Purkinje fibers. J Gen Physiol. 1977 Dec;70(6):725–746. doi: 10.1085/jgp.70.6.725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Giles W. R., van Ginneken A. C. A transient outward current in isolated cells from the crista terminalis of rabbit heart. J Physiol. 1985 Nov;368:243–264. doi: 10.1113/jphysiol.1985.sp015856. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Gögelein H. Chloride channels in epithelia. Biochim Biophys Acta. 1988 Oct 11;947(3):521–547. doi: 10.1016/0304-4157(88)90006-8. [DOI] [PubMed] [Google Scholar]
  28. HODGKIN A. L., HOROWICZ P. The influence of potassium and chloride ions on the membrane potential of single muscle fibres. J Physiol. 1959 Oct;148:127–160. doi: 10.1113/jphysiol.1959.sp006278. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. HODGKIN A. L., KATZ B. The effect of sodium ions on the electrical activity of giant axon of the squid. J Physiol. 1949 Mar 1;108(1):37–77. doi: 10.1113/jphysiol.1949.sp004310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. HUTTER O. F., NOBLE D. Anion conductance of cardiac muscle. J Physiol. 1961 Jul;157:335–350. doi: 10.1113/jphysiol.1961.sp006726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. HUTTER O. F., NOBLE D. The chloride conductance of frog skeletal muscle. J Physiol. 1960 Apr;151:89–102. [PMC free article] [PubMed] [Google Scholar]
  32. Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
  33. Harvey R. D., Hume J. R. Autonomic regulation of a chloride current in heart. Science. 1989 May 26;244(4907):983–985. doi: 10.1126/science.2543073. [DOI] [PubMed] [Google Scholar]
  34. Harvey R. D., Hume J. R. Autonomic regulation of delayed rectifier K+ current in mammalian heart involves G proteins. Am J Physiol. 1989 Sep;257(3 Pt 2):H818–H823. doi: 10.1152/ajpheart.1989.257.3.H818. [DOI] [PubMed] [Google Scholar]
  35. Harvey R. D., Ten Eick R. E. On the role of sodium ions in the regulation of the inward-rectifying potassium conductance in cat ventricular myocytes. J Gen Physiol. 1989 Aug;94(2):329–348. doi: 10.1085/jgp.94.2.329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Hescheler J., Kameyama M., Trautwein W. On the mechanism of muscarinic inhibition of the cardiac Ca current. Pflugers Arch. 1986 Aug;407(2):182–189. doi: 10.1007/BF00580674. [DOI] [PubMed] [Google Scholar]
  37. Hill J. A., Jr, Coronado R., Strauss H. C. Reconstitution of ionic channels from human heart. J Mol Cell Cardiol. 1989 Mar;21(3):315–322. doi: 10.1016/0022-2828(89)90747-5. [DOI] [PubMed] [Google Scholar]
  38. Hiraoka M., Hiraoka M. Effects of low temperature on the positive dynamic current of cardiac Purkinje fibres. J Physiol. 1973 Nov;234(3):587–595. doi: 10.1113/jphysiol.1973.sp010362. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Hiraoka M., Hiraoka M. The role of the positive dynamic current on the action potential of cardiac Purkinje fibers. Jpn J Physiol. 1975;25(6):705–717. doi: 10.2170/jjphysiol.25.705. [DOI] [PubMed] [Google Scholar]
  40. Hiraoka M., Kawano S. Calcium-sensitive and insensitive transient outward current in rabbit ventricular myocytes. J Physiol. 1989 Mar;410:187–212. doi: 10.1113/jphysiol.1989.sp017528. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Hume J. R., Uehara A., Hadley R. W., Harvey R. D. Comparison of K+ channels in mammalian atrial and ventricular myocytes. Prog Clin Biol Res. 1990;334:17–41. [PubMed] [Google Scholar]
  42. Hume J. R., Uehara A. Ionic basis of the different action potential configurations of single guinea-pig atrial and ventricular myocytes. J Physiol. 1985 Nov;368:525–544. doi: 10.1113/jphysiol.1985.sp015874. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. IJzerman A. P., Soudijn W. The antiarrhythmic properties of beta-adrenoceptor antagonists. Trends Pharmacol Sci. 1989 Jan;10(1):31–36. doi: 10.1016/0165-6147(89)90104-1. [DOI] [PubMed] [Google Scholar]
  44. Karwatowska-Kryńska E., Beresewicz A. Effect of locally released catecholamines on lipolysis and injury of the hypoxic isolated rabbit heart. J Mol Cell Cardiol. 1983 Aug;15(8):523–536. doi: 10.1016/0022-2828(83)90328-0. [DOI] [PubMed] [Google Scholar]
  45. Kenyon J. L., Gibbons W. R. 4-Aminopyridine and the early outward current of sheep cardiac Purkinje fibers. J Gen Physiol. 1979 Feb;73(2):139–157. doi: 10.1085/jgp.73.2.139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Kenyon J. L., Gibbons W. R. Effects of low-chloride solutions on action potentials of sheep cardiac Purkinje fibers. J Gen Physiol. 1977 Nov;70(5):635–660. doi: 10.1085/jgp.70.5.635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Kenyon J. L., Gibbons W. R. Influence of chloride, potassium, and tetraethylammonium on the early outward current of sheep cardiac Purkinje fibers. J Gen Physiol. 1979 Feb;73(2):117–138. doi: 10.1085/jgp.73.2.117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Matsuda H., Saigusa A., Irisawa H. Ohmic conductance through the inwardly rectifying K channel and blocking by internal Mg2+. Nature. 1987 Jan 8;325(7000):156–159. doi: 10.1038/325156a0. [DOI] [PubMed] [Google Scholar]
  49. Matsuura H., Ehara T., Imoto Y. An analysis of the delayed outward current in single ventricular cells of the guinea-pig. Pflugers Arch. 1987 Dec;410(6):596–603. doi: 10.1007/BF00581319. [DOI] [PubMed] [Google Scholar]
  50. Mayer M. L. A calcium-activated chloride current generates the after-depolarization of rat sensory neurones in culture. J Physiol. 1985 Jul;364:217–239. doi: 10.1113/jphysiol.1985.sp015740. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. McAllister R. E., Noble D., Tsien R. W. Reconstruction of the electrical activity of cardiac Purkinje fibres. J Physiol. 1975 Sep;251(1):1–59. doi: 10.1113/jphysiol.1975.sp011080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Nakayama T., Fozzard H. A. Adrenergic modulation of the transient outward current in isolated canine Purkinje cells. Circ Res. 1988 Jan;62(1):162–172. doi: 10.1161/01.res.62.1.162. [DOI] [PubMed] [Google Scholar]
  53. Nakayama T., Irisawa H. Transient outward current carried by potassium and sodium in quiescent atrioventricular node cells of rabbits. Circ Res. 1985 Jul;57(1):65–73. doi: 10.1161/01.res.57.1.65. [DOI] [PubMed] [Google Scholar]
  54. Nakayama T., Palfrey C., Fozzard H. A. Modulation of the cardiac transient outward current by catecholamines. J Mol Cell Cardiol. 1989 Feb;21 (Suppl 1):109–118. doi: 10.1016/0022-2828(89)90845-6. [DOI] [PubMed] [Google Scholar]
  55. Noma A., Nakayama T., Kurachi Y., Irisawa H. Resting K conductances in pacemaker and non-pacemaker heart cells of the rabbit. Jpn J Physiol. 1984;34(2):245–254. doi: 10.2170/jjphysiol.34.245. [DOI] [PubMed] [Google Scholar]
  56. Noma A., Shibasaki T. Membrane current through adenosine-triphosphate-regulated potassium channels in guinea-pig ventricular cells. J Physiol. 1985 Jun;363:463–480. doi: 10.1113/jphysiol.1985.sp015722. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Pacaud P., Loirand G., Lavie J. L., Mironneau C., Mironneau J. Calcium-activated chloride current in rat vascular smooth muscle cells in short-term primary culture. Pflugers Arch. 1989 Apr;413(6):629–636. doi: 10.1007/BF00581813. [DOI] [PubMed] [Google Scholar]
  58. Palade P. T., Barchi R. L. On the inhibition of muscle membrane chloride conductance by aromatic carboxylic acids. J Gen Physiol. 1977 Jun;69(6):879–896. doi: 10.1085/jgp.69.6.879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Peper K., Trautwein W. A membrane current related to the plateau of the action potential of Purkinje fibers. Pflugers Arch. 1968;303(2):108–123. doi: 10.1007/BF00592629. [DOI] [PubMed] [Google Scholar]
  60. Pidoplichko V. I., Verkhratsky A. N. Possible existence of transient TTX-sensitive chloride current in the membrane of isolated cardiomyocytes. Gen Physiol Biophys. 1987 Jun;6(3):223–235. [PubMed] [Google Scholar]
  61. Reuter H. Slow inactivation of currents in cardiac Purkinje fibres. J Physiol. 1968 Jul;197(1):233–253. doi: 10.1113/jphysiol.1968.sp008557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Sakmann B., Trube G. Conductance properties of single inwardly rectifying potassium channels in ventricular cells from guinea-pig heart. J Physiol. 1984 Feb;347:641–657. doi: 10.1113/jphysiol.1984.sp015088. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Sanguinetti M. C., Scott A. L., Zingaro G. J., Siegl P. K. BRL 34915 (cromakalim) activates ATP-sensitive K+ current in cardiac muscle. Proc Natl Acad Sci U S A. 1988 Nov;85(21):8360–8364. doi: 10.1073/pnas.85.21.8360. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Seamon K. B., Daly J. W. Forskolin: its biological and chemical properties. Adv Cyclic Nucleotide Protein Phosphorylation Res. 1986;20:1–150. [PubMed] [Google Scholar]
  65. Shah A. K., Cohen I. S., Datyner N. B. Background K+ current in isolated canine cardiac Purkinje myocytes. Biophys J. 1987 Oct;52(4):519–525. doi: 10.1016/S0006-3495(87)83241-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Siegelbaum S. A., Tsien R. W. Calcium-activated transient outward current in calf cardiac Purkinje fibres. J Physiol. 1980 Feb;299:485–506. doi: 10.1113/jphysiol.1980.sp013138. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Siegelbaum S. A., Tsien R. W., Kass R. S. Role of intracellular calcium in the transient outward current of calf Purkinje fibres. Nature. 1977 Oct 13;269(5629):611–613. doi: 10.1038/269611a0. [DOI] [PubMed] [Google Scholar]
  68. Soejima M., Kokubun S. Single anion-selective channel and its ion selectivity in the vascular smooth muscle cell. Pflugers Arch. 1988 Mar;411(3):304–311. doi: 10.1007/BF00585119. [DOI] [PubMed] [Google Scholar]
  69. Spitzer K. W., Walker J. L. Intracellular chloride activity in quiescent cat papillary muscle. Am J Physiol. 1980 Apr;238(4):H487–H493. doi: 10.1152/ajpheart.1980.238.4.H487. [DOI] [PubMed] [Google Scholar]
  70. Tseng G. N., Hoffman B. F. Two components of transient outward current in canine ventricular myocytes. Circ Res. 1989 Apr;64(4):633–647. doi: 10.1161/01.res.64.4.633. [DOI] [PubMed] [Google Scholar]
  71. VINCENZI F. F., WEST T. C. RELEASE OF AUTONOMIC MEDIATORS IN CARDIAC TISSUE BY DIRECT SUBTHRESHOLD ELECTRICAL STIMULATION. J Pharmacol Exp Ther. 1963 Aug;141:185–194. [PubMed] [Google Scholar]
  72. Vandenberg C. A. Inward rectification of a potassium channel in cardiac ventricular cells depends on internal magnesium ions. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2560–2564. doi: 10.1073/pnas.84.8.2560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Vaughan-Jones R. D. Non-passive chloride distribution in mammalian heart muscle: micro-electrode measurement of the intracellular chloride activity. J Physiol. 1979 Oct;295:83–109. doi: 10.1113/jphysiol.1979.sp012956. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Videbaek J., Christensen N. J., Sterndorff B. Serial determination of plasma catecholamines in myocardial infarction. Circulation. 1972 Nov;46(5):846–855. doi: 10.1161/01.cir.46.5.846. [DOI] [PubMed] [Google Scholar]
  75. Vitek M., Trautwein W. Slow inward current and action potential in cardiac Purkinje fibres. The effect of Mn plus,plus-ions. Pflugers Arch. 1971;323(3):204–218. doi: 10.1007/BF00586384. [DOI] [PubMed] [Google Scholar]
  76. Walsh K. B., Begenisich T. B., Kass R. S. Beta-adrenergic modulation of cardiac ion channels. Differential temperature sensitivity of potassium and calcium currents. J Gen Physiol. 1989 May;93(5):841–854. doi: 10.1085/jgp.93.5.841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. Wangemann P., Wittner M., Di Stefano A., Englert H. C., Lang H. J., Schlatter E., Greger R. Cl(-)-channel blockers in the thick ascending limb of the loop of Henle. Structure activity relationship. Pflugers Arch. 1986;407 (Suppl 2):S128–S141. doi: 10.1007/BF00584942. [DOI] [PubMed] [Google Scholar]
  78. Wiggins J. R., Cranefield P. F. Two levels of resting potential in canine cardiac Purkinje fibers exposed to sodium-free solutions. Circ Res. 1976 Oct;39(4):466–474. doi: 10.1161/01.res.39.4.466. [DOI] [PubMed] [Google Scholar]

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