Functional coupling of human L-type Ca2+ channels and angiotensin AT(1A) receptors coexpressed in Xenopus laevis oocytes: Involvement of the carboxyl-terminal Ca2+ sensors

O. Z. Murat, Michael T. Melia, Nikolai M. Soldatov, Darrell R. Abernethy, Martin Morad

Research output: Contribution to journalArticlepeer-review

Abstract

A human recombinant L-type Ca2+ channel (α(1C,77)) was coexpressed with the rat angiotensin AT(1A) receptor in Xenopus laevis oocytes. In oocytes expressing only α(1C,77) channels, application of human angiotensin II (1-10 μM) did not affect the amplitude or kinetics of Ba2+ currents (I(Ba)). In sharp contrast, in oocytes coexpressing α(1C,77) channels and AT(1A) receptors, application of 1 nM to 1 μM angiotensin gradually and reversibly inhibited I(Ba), without significantly changing its kinetics. The inhibitory effect of angiotensin on I(Ba) was abolished in oocytes that had been preincubated with losartan (an AT(1A) receptor antagonist) or thapsigargin or injected with 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'- tetraacetate, pertussis toxin, guanosine-5'-O-(2-thio)diphosphate, or heparin, suggesting that the recombinant α(1C) channels were regulated by angiotensin through G protein-coupled AT(1A) receptors via activation of the inositol trisphosphate-dependent intracellular Ca2+ release pathway. Consistent with this hypothesis, no cross-signaling occurred between the AT(1A) receptor and a splice variant of α(1C) lacking Ca2+ sensors (α(1C,86)). The data suggest that the regulation of recombinant L-type Ca2+ channels by angiotensin is mediated by inositol trisphosphate-induced intracellular Ca2+ release and occurs at the molecular motif responsible for the Ca2+induced inactivation of the channels.

Original languageEnglish (US)
Pages (from-to)1106-1112
Number of pages7
JournalMolecular Pharmacology
Volume54
Issue number6
DOIs
StatePublished - 1998

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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