APStracts 3:0050C, 1996.

Angiotensin ii type 1 receptor-modulation of neuronal k+ and ca2+ currents: intracellular mechanisms. Sumners, Colin, Mingyan Zhu, Craig Gelband, and Philip Posner. Department of Physiology, University of Florida, College of Medicine, PO Box 100274, Gainesville, FL 32610

APStracts 3:0050C, 1996.

Angiotensin II (Ang II) elicits an Ang II type 1 (AT1) receptor -mediated decrease in voltage-dependent K+ current (IK), and an increase in voltage-dependent Ca2+ current (ICa), in neurons co -cultured from newborn rat hypothalamus and brainstem. Modulation of these currents by Ang II involves intracellular messengers which result from an AT1 receptor-mediated stimulation of phosphoinositide hydrolysis. For example, the effects of Ang II on IK and ICa were abolished by phospholipase C antagonists. The reduction in IK produced by Ang II was attenuated by either protein kinase C (PKC) antagonists or by chelation of intracellular Ca2+. By contrast, PKC antagonism abolished the stimulatory effect of Ang II on ICa. Superfusion of the PKC activator phorbol-12-myristate-13-acetate produced effects on IK and ICa similar to those observed following Ang II. Furthermore, intracellular application of inositol [1,4,5] triphosphate (IP3) elicited a significant reduction in IK. This suggests that the AT1 receptor-mediated changes in neuronal K+ and Ca2+ currents involve PKC (both IK and ICa) and IP3/intracellular Ca2+ (IK).

Received 6 October 1995; accepted in final form 5 January 1996.
APS Manuscript Number C607-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 February 96