A-TYPE K-STEM - MODULATION BY ANGIOTENSIN-II( CURRENT IN NEURONS CULTURED FROM NEONATAL RAT HYPOTHALAMUS AND BRAIN)

The regulation of A-type KC current (IA) and the single channel underl ying IA in neonatal rat hypothalamus/brain stem cultured neurons were studied with the use of the patch-clamp technique. I, had a threshold of activation between -30 and -25 mV (n = 14). Steady-state inactivati on of IA occurred between -80 and -70 mV and had a membrane voltage at which IA was half-maximum of -52.2 mV (n = 14). The mean values for t he activation and inactivation (decay) time constants during a voltage step to +20 mV were 2.1 +/- 0.3 (SE) ms (n = 8) and 13.6 +/- 1.9 ms ( n = 8), respectively. Single-channel recordings from outside-out patch es revealed A-type K+ channels with voltage-dependent activation, 4-am inopyridine (4-AP) sensitivity, and inactivation kinetics similar to t hose of I-A. The single channel conductance obtained from cell-attache d patches was 15.8 +/- 1.3 pS (n = 4) in a physiological K+ gradient a nd 41.2 +/- 3.7 pS (n = 5) in symmetrical 140 mM K+. Angiotensin II (A ng II, 100 nM) reduced peak IA by similar to 20% during a voltage step to +20 mV (n = 8). Similarly, Ang II (100 nM) markedly reduced single A-type K+ channel activity by decreasing open probability (n = 4). Th e actions of Ang II on I-A and single A-type K+ channels were reversib le either by addition of the selective angiotensin type 1 (AT(1)) rece ptor antagonist losartan (1 mu M) or on washout of the peptide. Thus t he activation of AT(1) receptors inhibits a tetraethyl-ammonium-chlori de-resistant, 4-AP-sensitive I-A and single A-type K+ channels, and th is may underlie some of the actions of Ang II on electrical activity o f the brain.