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Defects in ryanodine receptor calcium release in skeletal muscle from postmyocardial infarcted rats
Author(s) -
Ward C. W.,
Reiken S.,
Marks A. R.,
Marty I.,
Vassort G.,
Lacampagne A.
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-1083fje
Subject(s) - ryr1 , ryanodine receptor , skeletal muscle , medicine , calcium , chemistry , calcium signaling , endocrinology , ryanodine receptor 2 , myocyte , muscle contraction , biology
Defective calcium (Ca 2+ ) signaling and impaired contractile function have been observed in skeletal muscle secondary to impaired myocardial function. However, the molecular basis for these muscle defects have not been identified. In this study, we evaluated the alterations of the ryanodine‐sensitive Ca 2+ release channels (RyR1) by analyzing global and local Ca 2+ signaling in a rat postmyocardial infarction (PMI) model of myocardial overload. Ca 2+ transients, measured with multiphoton imaging in individual fibers within a whole extensor digitorum longus (EDL) muscle, exhibited significantly reduced amplitude and a prolonged time course in PMI. Spatiotemporal properties of spontaneous Ca 2+ sparks in fibers isolated from PMI EDL muscles were also significantly altered. In addition, RyR1 from PMI skeletal muscles were PKA‐hyperphosphorylated and depleted of the FK506 binding protein (FKBP12). These data show that PMI skeletal muscles exhibit altered local Ca 2+ signaling, associated with hyperphosphorylation of RyR1. The observed changes in Ca 2+ signaling may contribute to defective excitation‐contraction coupling in muscle that can contribute to the reduced exercise capacity in PMI, out of proportion to the degree of cardiac dysfunction.