Ca2+-induced inhibition of the cardiac Ca2+ channel depends on calmodulin

Ca2+-induced inhibition of alpha(1C) voltage gated Ca2+ channels is a physi ologically important regulatory mechanism that shortens the mean open time of these otherwise long-lasting high-voltage-activated channels. The mechan ism of action of Ca2+ has been a matter of some controversy, as previous st udies have proposed the involvement of a putative Ca2+-binding EF hand in t he C terminus of alpha(1C) and/or a sequence downstream from this EF-hand m otif containing a putative calmodulin (CaM) binding IQ motif. Previously, u sing site directed mutagenesis, we have shown that disruption of the EF-han d motif does not remove Ca2+ inhibition. We now show that the IQ motif bind s 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.