Chloride conductance regulated by cyclic AMP-dependent protein kinase in cardiac myocytes

Abstract

IN heart cells, cyclic AMP-dependent protein kinase (PKA) regulates calcium-^1-4 and potassium-ion current^1,2,5,6 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 cells⁷. But, like epithelial Cl⁻-channel currents, the cardiac Cl⁻ current was sensitive to the distilbene, 4,4′-dinitrostilbene-2,2′-disulphonic acid (DNDS)⁸. In the absence of kinase activation, cardiac sarcolemmal C1⁻ conductance was negligible. During β-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.