CHARACTERIZATION OF AN ANGIOTENSIN-II-ACTIVATED CHLORIDE CURRENT IN RABBIT SINOATRIAL CELLS

Single sino-atrial cells from rabbit heart were voltage-clamped using the whole-cell configuration of the patch clamp technique under condit ions in which most of the ionic and exchange currents known in pacemak er cardiac cells were minimized. Extracellular angiotensin II (AII) ac tivated a time-independent background current. The current-voltage rel ation of this current showed an outward rectification. The reversal po tential was -20 mV with 156 mM Cl- external solution and 54 mM Cl- int ernal solution. This reversal potential shifted with changes in the tr ansmembrane Cl- gradient in the fashion expected for a chloride curren t. Anthracene-9-carboxylic acid and diphenylamine-2-carboxilic acid (c hloride channels blockers) were found to be effective in blocking the AII-sensitive current. The linear segment of the current-voltage relat ion can be totally inhibited by the competitive AII-receptor (AT1) ant agonist losartan and by the presence of intracellular protein kinase C inhibitor, whereas the outward rectification is only slightly changed . It is concluded that sino-atrial cells should contain proteinkinase- C-sensitive chloride channels which may be activated by angiotensin II via the stimulation of the AT1 receptors.