Ca²⁺-dependent regulation of sodium channels Na_V1.4 and Na_V1.5 is controlled by the post-IQ motif.

ABSTRACT: Skeletal muscle voltage-gated Na⁺ channel (Na_V1.4) activity is subject to calmodulin (CaM) mediated Ca²⁺-dependent inactivation; no such inactivation is observed in the cardiac Na⁺ channel (Na_V1.5). Taken together, the crystal structures of the Na_V1.4 C-terminal domain relevant complexes and thermodynamic binding data presented here provide a rationale for this isoform difference. A Ca²⁺-dependent CaM N-lobe binding site previously identified in Na_V1.5 is not present in Na_V1.4 allowing the N-lobe to signal other regions of the Na_V1.4 channel. Consistent with this mechanism, removing this binding site in Na_V1.5 unveils robust Ca²⁺-dependent inactivation in the

SUBMITTER: Yoder JB 

PROVIDER: S-EPMC6447637 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature