Angiotensin II suppresses Na+ currents in bovine adrenal chromaffin cells

We investigated the effects of angiotensin II (ANG II) on the voltage-dependent Na+ channel currents (INa) recorded from bovine adrenal medullary chromaffin cells (BCCs) under whole-cell voltage clamp. Angiotensin II reversibly reduced the peak INa in a dose-dependent fashion. Inhibition was observed at a concentration of 1 nM (6.3 +/- 1.4%, mean +/- SEM) and reached a maximum at 1 microM (35 +/- 3.8%), with a half-maximal effect at 11.6 nM. The ANG II-induced inhibition resulted from a reduction in peak conductance (control, 7.2 +/- 0.7 nS; ANG II 4.3 +/- 0.5 nS; p < 0.01). Angiotensin II had no effect on the reversal potential or the decay time of INa. In addition, the V1/2 and k values, two parameters that describe the voltage dependence of INa for both steady-state activation and inactivation, were not affected by ANG II. The response to ANG II (1 microM) had a delay and attained maximum inhibition in 0.9 +/- 0.2 min (n = 10). Recovery from the effect was slow and took 3.5 +/- 0.8 min (n = 10) after the application of ANG II had been terminated. The inhibitory effects of ANG II were effectively blocked by a specific ANG II receptor antagonist. [Sar1, Val5, Ala8]ANG II. The present study demonstrates that ANG II inhibits voltage-dependent INa+ channel currents in BCCs via a specific receptor-coupled mechanism. The prolonged time course of the ANG II response indicates a possible involvement of second messenger(s) mediating this inhibition.