XB-ART-13447Proc Natl Acad Sci U S A March 2, 1999; 96 (5): 2435-8.
Ca2+-induced inhibition of the cardiac Ca2+ channel depends on calmodulin.
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.
PubMed ID: 10051660
PMC ID: PMC26802
Article link: Proc Natl Acad Sci U S A
References [+] :
Biel, Primary structure and functional expression of a high voltage activated calcium channel from rabbit lung. 1990, Pubmed, Xenbase