Allosteric regulators selectively prevent Ca²⁺-feedback of Ca_V and Na_V channels.

ABSTRACT: Calmodulin (CaM) serves as a pervasive regulatory subunit of Ca_V1, Ca_V2, and Na_V1 channels, exploiting a functionally conserved carboxy-tail element to afford dynamic Ca²⁺-feedback of cellular excitability in neurons and cardiomyocytes. Yet this modularity counters functional adaptability, as global changes in ambient CaM indiscriminately alter its targets. Here, we demonstrate that two structurally unrelated proteins, SH3 and cysteine-rich domain (stac) and fibroblast growth factor homologous factors (fhf) selectively diminish Ca²⁺/CaM-regulation of Ca_V1 and Na_V1 families, respectively. The two proteins operate on allosteric sites within upstream portions of respective channel carboxy-tails, distinct from the CaM

SUBMITTER: Niu J 

PROVIDER: S-EPMC6156082 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature