Alterations in contractility and intracellular Ca2+ transients in isolated bundles of skeletal muscle fibers from rats with chronic heart failure.
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.
Perreault
C L
CL
Charles A. Dana Research Institute, Boston, MA.
Gonzalez-Serratos
H
H
Litwin
S E
SE
Sun
X
X
Franzini-Armstrong
C
C
Morgan
J P
JP
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
D000331:Aequorin; D002118:Calcium