Pore mutation N617D in the skeletal muscle DHPR blocks Ca²⁺ influx due to atypical high-affinity Ca²⁺ binding.

ABSTRACT: Skeletal muscle excitation-contraction (EC) coupling roots in Ca²⁺-influx-independent inter-channel signaling between the sarcolemmal dihydropyridine receptor (DHPR) and the ryanodine receptor (RyR1) in the sarcoplasmic reticulum. Although DHPR Ca²⁺ influx is irrelevant for EC coupling, its putative role in other muscle-physiological and developmental pathways was recently examined using two distinct genetically engineered mouse models carrying Ca²⁺ non-conducting DHPRs: DHPR(N617D) (Dayal et al., 2017) and DHPR(E1014K) (Lee et al., 2015). Surprisingly, despite complete block of DHPR Ca²⁺-conductance, histological, biochemical, and physiological results obtained from these two models were contradictory. Here, we characterize the permeability and

SUBMITTER: Dayal A 

PROVIDER: S-EPMC8184209 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature