Loss of Calpain 3 dysregulates store-operated calcium entry and its exercise response in mice.

ABSTRACT: Limb-Girdle Muscular Dystrophy R1/2A (LGMD R1/2A) is caused by mutations in the CAPN3 gene encoding Calpain 3, a skeletal-muscle specific, Ca²⁺-dependent protease. Localization of Calpain 3 within the triad suggests it contributes to Ca²⁺ homeostasis. Through live-cell Ca²⁺ measurements, muscle mechanics, immunofluorescence, and electron microscopy (EM) in Capn3 deficient (C3KO) and wild-type (WT) mice, we determined whether loss of Calpain 3 altered Store-Operated Calcium Entry (SOCE) activity. Direct Ca²⁺ influx measurements revealed loss of Capn3 elicits elevated resting SOCE and increased resting cytosolic Ca²⁺, supported by high incidence of calcium entry units (CEUs) observed by EM. C3KO and WT mice were subjected to a single bou

SUBMITTER: Villani KR 

PROVIDER: S-EPMC11299996 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature