Modulation of K+ and Ca2+ currents in cultured neurons by an angiotensin II type 1a receptor peptide
Zhu, M.; Neubig, R.R.; Wade, S.M.; Posner, P.; Gelband, C.H.; Sumners, C.
American Journal of Physiology 273(3 Pt 1): C1040-C1048
1997
ISSN/ISBN: 0002-9513 PMID: 9316425 Document Number: 478977
Angiotensin II (ANG II) inhibits delayed rectifier K+ current (I-K) and stimulates total Ca-2+ current (I-Ca) in neurons cocultured from newborn rat hypothalamus and brain stem, effects mediated via ANG II type 1 (AT-1) receptors. Here, we identify potential G protein activator regions of the AT-1 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 AT-1 receptor (AT-1a/i3) mimicked the actions of ANG II on I-K and I-Ca, whereas application of a peptide corresponding to the second cytoplasmic loop (AT-1a/i2) did not alter these currents. This modulation of I-K and I-Ca by AT-1a/i3 involves intracellular messengers (G-alpha-q, protein kinase C, and intracellular Ca-2+)that are identical to those involved in the modulation of I-K and I-Ca following ANG II activation of AT-1 receptors. These data provide functional evidence for a role of the third cytoplasmic loop of the AT-1 receptor in G protein coupling and subsequent modulation of ion channel effectors.