Characterization of an angiotensin-II-activated chloride current in rabbit sino-atrial cells

Single sino-atrial cells from rabbit heart were voltage-clamped using the whole-cell configuration of the patch clamp technique under conditions in which most of the ionic and exchange currents known in pacemaker cardiac cells were minimized. Extracellular angiotensin II (AII) activated a time-independent background current. The current-voltage relation of this current showed an outward rectification. The reversal potential was -20 mV with 156 mM Cl- external solution and 54 mM Cl- internal solution. This reversal potential shifted with changes in the transmembrane Cl- gradient in the fashion expected for a chloride current. Anthracene-9-carboxylic acid and diphenylamine-2-carboxylic acid (chloride channels blockers) were found to be effective in blocking the AII-sensitive current. The linear segment of the current-voltage relation can be totally inhibited by the competitive AII-receptor (AT1) antagonist 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 protein-kinase-C-sensitive chloride channels which may be activated by angiotensin II via the stimulation of the AT1 receptors.