A V-to-F substitution in SK2 channels causes Ca²⁺ hypersensitivity and improves locomotion in a C. elegans ALS model.

ABSTRACT: Small-conductance Ca²⁺-activated K⁺ (SK) channels mediate medium afterhyperpolarization in the neurons and play a key role in the regulation of neuronal excitability. SK channels are potential drug targets for ataxia and Amyotrophic Lateral Sclerosis (ALS). SK channels are activated exclusively by the Ca²⁺-bound calmodulin. Previously, we identified an intrinsically disordered fragment that is essential for the mechanical coupling between Ca²⁺/calmodulin binding and channel opening. Here, we report that substitution of a valine to phenylalanine (V407F) in the intrinsically disordered fragment caused a ~6 fold increase in the Ca²⁺ sensitivity of SK2-a channels. This substitution resulted in a novel interaction between the ectopic phenyl

SUBMITTER: Nam YW 

PROVIDER: S-EPMC6048120 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature