Channelpedia

PubMed 25370050


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Nav1 , Nav1.5



Title: Regulation of the NaV1.5 cytoplasmic domain by calmodulin.

Authors: Sandra B Gabelli, Agedi Boto, Victoria Halperin Kuhns, Mario A Bianchet, Federica Farinelli, Srinivas Aripirala, Jesse Yoder, Jean Jakoncic, Gordon F Tomaselli, L Mario Amzel

Journal, date & volume: Nat Commun, 2014 , 5, 5126

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25370050


Abstract
Voltage-gated sodium channels (Na(v)) underlie the rapid upstroke of action potentials in excitable tissues. Binding of channel-interactive proteins is essential for controlling fast and long-term inactivation. In the structure of the complex of the carboxy-terminal portion of Na(v)1.5 (CTNa(v)1.5) with calmodulin (CaM)-Mg(2+) reported here, both CaM lobes interact with the CTNa(v)1.5. On the basis of the differences between this structure and that of an inactivated complex, we propose that the structure reported here represents a non-inactivated state of the CTNa(v), that is, the state that is poised for activation. Electrophysiological characterization of mutants further supports the importance of the interactions identified in the structure. Isothermal titration calorimetry experiments show that CaM binds to CTNa(v)1.5 with high affinity. The results of this study provide unique insights into the physiological activation and the pathophysiology of Na(v) channels.