ANGIOTENSIN-II ACTIVATION OF A CHLORIDE CURRENT IN RABBIT CARDIAC MYOCYTES

1. The effects of angiotensin II (Ang II) on membrane currents were in vestigated in single ventricular myocytes from the rabbit heart by the whole-cell voltage-clamp method. 2. In the presence of an inhibitor o f Ca2+ currents (nifedipine at 3 mu M or CdCl2, at 0.3 mM) and a beta- adrenoceptor blocker (bupranolol at 1 mu M), 1 mu M Ang II significant ly increased the membrane conductance. 3. After elimination of K+ from external and internal solutions and its replacement by Cs+, Ang II at 0.1 mu M increased an outwardly rectifying current that reached a max imum after about 40 min. The effect was concentration dependent (10(-9 )-10(-6) nr) and was inhibited by saralasin, an antagonist of Ang II r eceptors. 4. The reversal potential of the Ang II-induced current in t he absence of K+ was compatible with the Cl- equilibrium potential at various external concentrations of Cl-. 5. A Cl- channel blocker, 4,4' -dinitrostilbene-2,2'-disulphonic acid (DNDS, at 5 mM), reversibly dec reased the Ang II-induced current. 6. The Ang II-induced current devel oped when the internal solution contained Ca2+ (pCa 7.2 or 7.0) but no t when it contained 10 mM EGTA without Ca2+. 7. Besides developing a C l- current, Ang II at 1 mu M increased the inwardly rectifying K+ curr ent (I-K1) and this effect reached maximum within 3 min. 8. The effect of Ang II on the action potential was biphasic: the duration of the a ction potential was initially reduced and then it was increased. 9. Th ese results suggest that Ang II induces a Cl- current that appears lik ely to modulate the action potential in rabbit ventricular myocytes.