A-type K super(+) current in neurons cultured from neonatal rat hypothalamus and brain stem: Modulation by angiotensin II

• Published in: Journal of neurophysiology 1997-08, Vol.78 (2), p.1021-1029
• Main Authors: Wang, Desuo, Sumners, C, Posner, P, Gelband, CH
• Format: Article
• Language: English
• ISSN: 0022-3077

The regulation of A-type K super(+) current (I sub(A)) and the single channel underlying I sub(A) in neonatal rat hypothalamus/brain stem cultured neurons were studied with the use of the patch-clamp technique. I sub(A) had a threshold of activation between -30 and -25 mV (n = 14). Steady-state inactivation of I sub(A) occurred between -80 and -70 mV and had a membrane voltage at which I sub(A) was half-maximum of -52.2 mV (n = 14). The mean values for the activation and inactivation (decay) time constants during a voltage step to +20 mV were 2.1 plus or minus 0.3 (SE) ms (n = 8) and 13.6 plus or minus 1.9 ms (n = 8), respectively. Single-channel recordings from outside-out patches revealed A-type K super(+) channels with voltage-dependent activation, 4-aminopyridine (4-AP) sensitivity, and inactivation kinetics similar to those of I sub(A). The singlechannel conductance obtained from cell-attached patches was 15.8 plus or minus 1.3 pS (n = 4) in a physiological K super(+) gradient and 41.2 plus or minus 3.7 pS (n = 5) in symmetrical 140 mM K super(+). Angiotensin II (Ang II, 100 nM) reduced peak I sub(A) by similar to 20% during a voltage step to +20 mV (n = 8). Similarly, Ang II (100 nM) markedly reduced single A-type K super(+) channel activity by decreasing open probability (n = 4). The actions of Ang II on I sub(A) and single A-type K super(+) channels were reversible either by addition of the selective angiotensin type 1 (AT sub(1)) receptor antagonist losartan (1 mu M) or on washout of the peptide. Thus the activation of AT sub(1) receptors inhibits a tetraethylammonium-chloride-resistant, 4-AP-sensitive I sub(A) and single A-type K super(+) channels, and this may underlie some of the actions of Ang II on electrical activity of the brain.