Interactions of Calmodulin With the Multiple Binding Sites of Cav1.2 Ca²⁺ Channels

Abstract

Although calmodulin binding to various sites of the Cav1.2 Ca²⁺ channel has been reported, the mechanism of the interaction is not fully understood. In this study we examined calmodulin binding to fragment channel peptides using a semi-quantitative pull-down assay. Calmodulin bound to the peptides with decreasing affinity order: IQ > preIQ > I-II loop > N-terminal peptide. A peptide containing both preIQ and IQ regions (Leu¹⁵⁹⁹ – Leu¹⁶⁶⁸) bound with approximately 2 mol of calmodulin per peptide. These results support the hypothesis that two molecules of calmodulin can simultaneously bind to the C-terminus of the Cav1.2 channel and modulate its facilitatory and inhibitory activities.