Re-examination of Na+-dependent regulation of cAMP-dependent Cl- currents in the heart.
Cardiac Cl- channels may play an important role in both the physiological as well as the pathophysiological regulation of the heart. Due to the present controversy regarding the role that Na+ may play in the regulation of the adenosine 3',5'-cyclic monophosphate (cAMP)-dependent Cl- channels in the heart, we have re-examined the effects of intracellular and extracellular Na+ on ICl,cAMP in isolated guinea-pig ventricular myocytes. In conventional, whole-cell patch-clamp experiments, exchanging of extracellular Na+ for N-methyl-d-glucamine (NMG) did not have a significant effect on the magnitude of the ICl,cAMP activated by external forskolin (FSK) in the presence of beta-adrenergic and muscarinic receptor blockade compared with normal rundown of the current with time. Utilization of the amphotericin B-perforated-patch technique prevented rundown of FSK-stimulated ICl, cAMP, and failed to reveal alterations in this conductance when NMG was substituted for extracellular Na+. Finally, intracellular dialysis of cells during whole-cell experiments with both 0 and 10 mM Na+-containing solutions failed to show any significant effect of intracellular Na+ on the magnitude of ICl,cAMP. We therefore conclude that intracellular or extracellular Na+ plays little or no direct regulatory role in modulation of cAMP-dependent Cl- channels in heart.
Warth
J D
JD
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Manville Medical Buildung/351, Reno, NV 89557-0046, USA.
Hume
J R
JR
D000818:Animals; D002118:Calcium / Q000378:metabolism; D018118:Chloride Channels / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D006168:Guinea Pigs; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*
D018118:Chloride Channels; D015221:Potassium Channels; D005576:Colforsin; D012964:Sodium; D000242:Cyclic AMP; D002118:Calcium