Alterations in the calcium homeostasis of skeletal muscle from postmyocardial infarcted rats.
In chronic heart failure, skeletal muscles develop a weakness that is not associated to an impaired circulatory function but rather to alterations in the skeletal muscle fibers themselves. To understand these changes, the steps in excitation-contraction coupling of rats that underwent a left anterior coronary artery occlusion were studied. About 24 weeks after the myocardial infarction, neither the total amount nor the voltage dependence of intramembrane charge were altered. In contrast, calcium release from the sarcoplasmic reticulum was considerably suppressed, and its voltage dependence shifted toward more positive voltages. Elementary calcium-release events showed altered morphology as the relative proportion of embers increased. Calcium sparks were smaller in amplitude and had larger time-to-peak values. Isolated ryanodine receptors (RyR) displayed an unusual rectification with increased single-channel conductance at positive (cis vs trans) voltages. In addition, the bell-shaped calcium dependence of channel activity was broader, with a slight shift of activation to lower and a larger shift in inactivation to higher calcium concentrations. These data indicate that the number of channels that open during a calcium-release event is decreased and that RyR function is altered; thus, calcium-release is suppressed after a myocardial infarction. These observations give an explanation for the impaired skeletal muscle function in these animals.
Szigeti
Gyula Péter
GP
Department of Physiology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
Almássy
János
J
Sztretye
Mónika
M
Dienes
Beatrix
B
Szabó
László
L
Szentesi
Péter
P
Vassort
Guy
G
Sárközi
Sándor
S
Csernoch
László
L
Jóna
István
I
D000818:Animals; D002118:Calcium / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology; D004594:Electrophysiology; D006706:Homeostasis / Q000502:physiology*; D008297:Male; D018656:Muscle Fibers, Fast-Twitch / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology*; D009203:Myocardial Infarction / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects; D012519:Sarcoplasmic Reticulum / Q000502:physiology
D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium