Ca2+-induced Inhibition of the Cardiac Ca2+ Channel Depends on Calmodulin

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1999 Mar 3

PMID 10051660

Citations 112

Authors

N Qin

R Olcese

M Bransby

T Lin

L Birnbaumer

Affiliations

Soon will be listed here.

Abstract

Ca2+-induced inhibition of alpha1C voltage-gated Ca2+ channels is a physiologically important regulatory mechanism that shortens the mean open time of these otherwise long-lasting high-voltage-activated channels. The mechanism of action of Ca2+ has been a matter of some controversy, as previous studies have proposed the involvement of a putative Ca2+-binding EF hand in the C terminus of alpha1C and/or a sequence downstream from this EF-hand motif containing a putative calmodulin (CaM)-binding IQ motif. Previously, using site directed mutagenesis, we have shown that disruption of the EF-hand motif does not remove Ca2+ inhibition. We now show that the IQ motif binds CaM and that disruption of this binding activity prevents Ca2+ inhibition. We propose that Ca2+ entering through the voltage-gated pore binds to CaM and that the Ca/CaM complex is the mediator of Ca2+ inhibition.

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