Chloride current in mammalian cardiac myocytes. Novel mechanism for autonomic regulation of action potential duration and resting membrane potential.
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.
Harvey
R D
RD
Department of Physiology, University of Nevada School of Medicine, Reno 89557.
Clark
C D
CD
Hume
J R
JR
D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000187:drug effects / Q000502:physiology*; D018118:Chloride Channels; D002712:Chlorides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000242:Cyclic AMP / Q000502:physiology; D004553:Electric Conductivity / Q000187:drug effects; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008564:Membrane Potentials / Q000502:physiology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors; D009206:Myocardium / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology
D018118:Chloride Channels; D002712:Chlorides; D008565:Membrane Proteins; D001285:Atropine; D011433:Propranolol; D000242:Cyclic AMP; D007545:Isoproterenol; D000109:Acetylcholine