title: Alterations in contractility and intracellular Ca2+ transients in isolated bundles of skeletal muscle fibers from rats with chronic heart failure.
abstract: To determine if chronic heart failure (CHF) leads to functional or structural alterations of skeletal muscle, we compared intracellular Ca2+ signaling, contractility, and the rate of fatigue development, together with electron microscopy (EM), in skeletal muscle preparations from rats with myocardial infarction-induced CHF versus sham-operated control rats. Bundles of 100 to 200 cells were dissected from the extensor digitorum longus (EDL) muscle of control (n = 13) and CHF (n = 19) rats and were either loaded with aequorin or fixed for EM. Muscles from CHF rats exhibited depressed tension development compared with control muscles during twitches (1.4 +/- 0.2 versus 2.8 +/- 0.7 g/mm2, P < .05) and maximal tetani (5.3 +/- 1.4 versus 10.7 +/- 2.4 g/mm2, P < .05). Depressed tension in CHF was accompanied by reduced quantitative [Ca2+]i release during twitches (0.7 +/- 0.1 versus 0.4 +/- 0.1 microM, P < .05) and during maximal tetani (1.8 +/- 0.3 versus 0.9 +/- 0.2 microM, P < .05). Skeletal muscle from CHF rats also demonstrated prolonged intracellular Ca2+ transients during twitches and tetani and accelerated fatigue development. EM revealed a lack of cellular atrophy in the CHF rats. In conclusion, EDL skeletal muscle from rats with CHF had intrinsic abnormalities in excitation-contraction coupling unrelated to cellular atrophy. These findings indicate that CHF is a condition accompanied by EDL skeletal muscle dysfunction.
authors.affiliation: Charles A. Dana Research Institute, Boston, MA.
authors.forename: C L
authors.initials: CL
authors.lastname: Perreault
authors.forename: H
authors.initials: H
authors.lastname: Gonzalez-Serratos
authors.forename: S E
authors.initials: SE
authors.lastname: Litwin
authors.forename: X
authors.initials: X
authors.lastname: Sun
authors.forename: C
authors.initials: C
authors.lastname: Franzini-Armstrong
authors.forename: J P
authors.initials: JP
authors.lastname: Morgan
mesh_terms: D000331:Aequorin / Q000494:pharmacology; D000818:Animals; D001284:Atrophy; D002118:Calcium / Q000502:physiology*; D002303:Cardiac Output, Low / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D002908:Chronic Disease; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism*; D008854:Microscopy, Electron; D009132:Muscles / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009200:Myocardial Contraction; D051381:Rats
chemical_list: D000331:Aequorin; D002118:Calcium