Impaired calcium signaling in muscle fibers from intercostal and foot skeletal muscle in a cigarette smoke-induced mouse model of COPD

Introduction: Respiratory and locomotor skeletal muscle dysfunction are common findings in chronic obstructive pulmonary disease (COPD); however, the mechanisms that cause muscle impairment in COPD are unclear. Because Ca²⁺ signaling in excitation–contraction (E-C) coupling is important for muscle activity, we hypothesized that Ca²⁺ dysregulation could contribute to muscle dysfunction in COPD. Methods: Intercostal and flexor digitorum brevis muscles from control and cigarette smoke-exposed mice were investigated. We used single cell Ca²⁺ imaging and Western blot assays to assess Ca²⁺ signals and E-C coupling proteins. Results: We found impaired Ca²⁺ signals in muscle fibers from both muscle types, without significant changes in releasable Ca²⁺ or in the expression levels of E-C coupling proteins. Conclusions: Ca²⁺ dysregulation may contribute or accompany respiratory and locomotor muscle dysfunction in COPD. These findings are of significance to the understanding of the pathophysiological course of COPD in respiratory and locomotor muscles. Muscle Nerve 56: 282–291, 2017.