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 (I-Na) recorded from bovine adrenal med ullary chromaffin cells (BCCs) under whole-cell voltage clamp. Angiote nsin II reversibly reduced the peak I-Na 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 mu M(35 +/- 3.8%), with a half-ma ximal 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 pote ntial or the decay time of I-Na. In addition, the V-1/2 and k values, two parameters that describe the voltage dependence of I-Na for both s teady-state activation and inactivation, were not affected by ANG II, The response to ANG II (1 mu M) had a delay and attained maximum inhib ition in 0.9 +/- 0.2 min (n = 10). Recovery from the effect was slow a nd took 3.5 +/- 0.8 min (n = 10) after the application of ANG II had b een terminated. The inhibitory effects of ANG II were effectively bloc ked by a specific ANG II receptor antagonist, [Sar(1),Val(5),Ala(8)]AN G II. The present study demonstrates that ANG II inhibits voltage-depe ndent I-Na+ channel currents in BCCs via a specific receptor-coupled m echanism. The prolonged time course of the ANG II response indicates a possible involvement of second messenger(s) mediating this inhibition .