Mitochondrial Calcium Uptake Regulates Rapid Calcium Transients in Skeletal Muscle during Excitation-Contraction (E-C) Coupling

• DOI: 10.1074/jbc.m110.217711
• Publication Date: 2011-07-28T04:21:48Z
• Authors: Jianxun Yi; Changling Ma; Yan Li; Noah Weisleder; Eduardo Ríos; Jianjie Ma; Jingsong Zhou
• Keywords: Calcium Signaling

Defective coupling between sarcoplasmic reticulum and mitochondria during control of intracellular Ca2+ signaling has been implicated in the progression neuromuscular diseases. Our previous study showed that skeletal muscles derived from an amyotrophic lateral sclerosis (ALS) mouse model displayed segmental loss mitochondrial function was coupled with elevated uncontrolled release activity. The localized defect ALS muscle allows for examination contribution to removal excitation-contraction by comparing transients regions normal defective same fiber. Here we show elicited membrane depolarization fiber segments display ∼10% increased amplitude. These regional differences were abolished application 1,2-bis(O-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid, a fast chelator reduces uptake. Using mitochondria-targeted biosensor (mt11-YC3.6) expressed fibers, monitored dynamic change levels voltage-induced detected reduced uptake segment mitochondria, which mirrored cytosol. constitutes direct demonstration importance shaping cytosolic establishes malfunction this mechanism may contribute degeneration ALS.