AJP - Cell Physiology, Vol 273, Issue 3 C1040-C1048, Copyright © 1997 by American Physiological Society

ARTICLES

Modulation of K+ and Ca2+ currents in cultured neurons by an angiotensin II type 1a receptor peptide

M. Zhu, R. R. Neubig, S. M. Wade, P. Posner, C. H. Gelband and C. Sumners
Department of Physiology, College of Medicine, University of Florida, Gainesville 32610, USA.

Angiotensin II (ANG II) inhibits delayed rectifier K+ current (IK) and stimulates total Ca2+ current (ICa) in neurons cocultured from newborn rat hypothalamus and brain stem, effects mediated via ANG II type 1 (AT1) receptors. Here, we identify potential G protein activator regions of the AT1 receptor responsible for initiating the intracellular changes that lead to alterations in these currents. Intracellular application into cultured neurons of a peptide corresponding to the third cytoplasmic loop of the AT1 receptor (AT1a/i3) mimicked the actions of ANG II on IK and ICa, whereas application of a peptide corresponding to the second cytoplasmic loop (AT1a/i2) did not alter these currents. This modulation of IK and ICa by AT1a/i3 involves intracellular messengers (G alpha q, protein kinase C, and intracellular Ca2+) that are identical to those involved in the modulation of IK and ICa following ANG II activation of AT1 receptors. These data provide functional evidence for a role of the third cytoplasmic loop of the AT1 receptor in G protein coupling and subsequent modulation of ion channel effectors.

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