Mechanisms Responsible for ω-Pore Currents in Ca_v Calcium Channel Voltage-Sensing Domains.

ABSTRACT: Mutations of positively charged amino acids in the S4 transmembrane segment of a voltage-gated ion channel form ion-conducting pathways through the voltage-sensing domain, named ω-current. Here, we used structure modeling and MD simulations to predict pathogenic ω-currents in Ca_V1.1 and Ca_V1.3 Ca²⁺ channels bearing several S4 charge mutations. Our modeling predicts that mutations of Ca_V1.1-R1 (R528H/G, R897S) or Ca_V1.1-R2 (R900S, R1239H) linked to hypokalemic periodic paralysis type 1 and of Ca_V1.3-R3 (R990H) identified in aldosterone-producing adenomas conducts ω-currents in resting state, but not during voltage-sensing domain activation. The mechanism responsible for the ω-current and its amplitude depend on the number of

SUBMITTER: Monteleone S 

PROVIDER: S-EPMC5627182 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature