Angiotensin II activation of a chloride current in rabbit cardiac myocytes.

1. The effects of angiotensin II (Ang II) on membrane currents were investigated in single ventricular myocytes from the rabbit heart by the whole-cell voltage-clamp method. 2. In the presence of an inhibitor of Ca2+ currents (nifedipine at 3 microM or CdCl2 at 0.3 mM) and a beta-adrenoceptor blocker (bupranolol at 1 microM), 1 microM Ang II significantly increased the membrane conductance. 3. After elimination of K+ from external and internal solutions and its replacement by Cs+, Ang II at 0.1 microM increased an outwardly rectifying current that reached a maximum after about 40 min. The effect was concentration dependent (10(-9)-10(-6) M) and was inhibited by saralasin, an antagonist of Ang II receptors. 4. The reversal potential of the Ang II-induced current in the 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 decreased the Ang II-induced current. 6. The Ang II-induced current developed when the internal solution contained Ca2+ (pCa 7.2 or 7.0) but not when it contained 10 mM EGTA without Ca2+. 7. Besides developing a Cl- current, Ang II at 1 microM increased the inwardly rectifying K+ current (IK1) and this effect reached maximum within 3 min. 8. The effect of Ang II on the action potential was biphasic: the duration of the action potential was initially reduced and then it was increased. 9. These results suggest that Ang II induces a Cl- current that appears likely to modulate the action potential in rabbit ventricular myocytes.