RT Journal Article
SR Electronic
T1 Functional Coupling of Human <span class="sc">L</span>-Type Ca<sup>2+</sup>Channels and Angiotensin AT<sub>1A</sub> Receptors Coexpressed in<em>Xenopus laevis</em> Oocytes: Involvement of the Carboxyl-Terminal Ca<sup>2+</sup> Sensors
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 1106
OP 1112
DO 10.1124/mol.54.6.1106
VO 54
IS 6
A1 Murat Oz
A1 Michael T. Melia
A1 Nikolai M. Soldatov
A1 Darrell R. Abernethy
A1 Martin Morad
YR 1998
UL http://molpharm.aspetjournals.org/content/54/6/1106.abstract
AB A human recombinant L-type Ca2+ channel (α1C,77) was coexpressed with the rat angiotensin AT1A receptor in Xenopus laevis oocytes. In oocytes expressing only α1C,77 channels, application of human angiotensin II (1–10 μm) did not affect the amplitude or kinetics of Ba2+ currents (IBa). In sharp contrast, in oocytes coexpressing α1C,77channels and AT1A receptors, application of 1 nm to 1 μm angiotensin gradually and reversibly inhibited IBa, without significantly changing its kinetics. The inhibitory effect of angiotensin on IBawas abolished in oocytes that had been preincubated with losartan (an AT1A 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 α1C channels were regulated by angiotensin through G protein-coupled AT1A receptors via activation of the inositol trisphosphate-dependent intracellular Ca2+ release pathway. Consistent with this hypothesis, no cross-signaling occurred between the AT1A receptor and a splice variant of α1Clacking Ca2+ sensors (α1C,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.