Chloride conductance regulated by cyclic AMP-dependent protein kinase in cardiac myocytes.
In heart cells, cyclic AMP-dependent protein kinase (PKA) regulates calcium- and potassium-ion current by phosphorylating the ion channels or closely associated regulatory proteins. We report here that isoprenaline induced large chloride-ion currents in voltage-clamped, internally-dialysed myocytes from guinea-pig ventricles. The Cl- current could be activated by intracellular dialysis with cAMP or the catalytic subunit of PKA, indicating regulation by phosphorylation. In approximately symmetrical solutions of high Cl- concentration, the macroscopic cardiac Cl- current showed little rectification, unlike the single-channel current in PKA-regulated Cl- channels of airway epithelial cells. But, like epithelial Cl- -channel currents, the cardiac Cl- current was sensitive to the distilbene,4,4'-dinitrostilbene-2,2'-disulphonic acid (DNDS). In the absence of kinase activation, cardiac sarcolemmal Cl- conductance was negligible. During beta-adrenergic stimulation of the heart, this novel Cl- conductance should accelerate action-potential repolarization and so protect impulse propagation in the face of the possibly arrhythmogenic increases in heart rate and in calcium entry into the cells.
Bahinski
A
A
Laboratory of Cardiac Physiology, Rockefeller University, New York 10021.
Nairn
A C
AC
Greengard
P
P
Gadsby
D C
DC
D000818:Animals; D002712:Chlorides / Q000502:physiology*; D000242:Cyclic AMP / Q000502:physiology*; D004553:Electric Conductivity; D006168:Guinea Pigs; D006329:Heart Conduction System / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D006352:Heart Ventricles / Q000201:enzymology; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000201:enzymology*; D011494:Protein Kinases / Q000502:physiology*; D016276:Ventricular Function
D002712:Chlorides; D007473:Ion Channels; D000242:Cyclic AMP; D011494:Protein Kinases; D007545:Isoproterenol