A-type K+ current in neurons cultured from neonatal rat hypothalamus and brain stem: modulation by angiotensin II.
The regulation of A-type K+ current (I(A)) and the single channel underlying I(A) in neonatal rat hypothalamus/brain stem cultured neurons were studied with the use of the patch-clamp technique. I(A) had a threshold of activation between -30 and -25 mV (n = 14). Steady-state inactivation of I(A) occurred between -80 and -70 mV and had a membrane voltage at which I(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 +/- 0.3 (SE) ms (n = 8) and 13.6 +/- 1.9 ms (n = 8), respectively. Single-channel recordings from outside-out patches revealed A-type K+ channels with voltage-dependent activation, 4-aminopyridine (4-AP) sensitivity, and inactivation kinetics similar to those of I(A). The single-channel conductance obtained from cell-attached patches was 15.8 +/- 1.3 pS (n = 4) in a physiological K+ gradient and 41.2 +/- 3.7 pS (n = 5) in symmetrical 140 mM K+. Angiotensin II (Ang II, 100 nM) reduced peak I(A) by approximately 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). The actions of Ang II on I(A) and single A-type K+ channels were reversible either by addition of the selective angiotensin type 1 (AT1) receptor antagonist losartan (1 microM) or on washout of the peptide. Thus the activation of AT1 receptors inhibits a tetraethylammonium-chloride-resistant, 4-AP-sensitive I(A) and single A-type K+ channels, and this may underlie some of the actions of Ang II on electrical activity of the brain.
Wang
D
D
Department of Physiology, University of Florida College of Medicine, Gainesville 32610, USA.
Sumners
C
C
Posner
P
P
Gelband
C H
CH
D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D055592:Biophysical Phenomena; D001703:Biophysics; D001933:Brain Stem / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D015221:Potassium Channels; D000804:Angiotensin II; D015761:4-Aminopyridine