Ca-induced Ca release in malignant hyperthermia-susceptible pig skeletal muscle.
To provide information regarding the cause of the muscle rigidity in malignant hyperthermia-susceptible (MHS) pigs, the Ca-induced Ca-release mechanism of the sarcoplasmic reticulum (SR), the Ca uptake by the SR, and the Ca-activated tension production of the contractile system were examined in skinned skeletal muscle fibers from MHS and normal pigs. In muscles of MHS pigs, the rate of Ca-induced Ca release was significantly higher than in normal muscle. The potentiation effect on Ca-induced Ca release by halothane and caffeine did not differ appreciably between MHS and normal fibers. The rate of Ca uptake by the SR and the Ca sensitivity of the contractile system of MHS fibers were not different from those of normal fibers, and halothane in an anesthetic concentration exerted no effect on them. Dantrolene inhibited the Ca-induced Ca release at 38 degrees C. These results suggest that the principal cause of malignant hyperthermia (MH) in MHS pigs is due to the enhancement of the Ca-induced Ca-release mechanism of the SR of the skeletal muscle.
Ohta
T
T
Department of Pharmacology, Faculty of Medicine, University of Tokyo, Japan.
Endo
M
M
Nakano
T
T
Morohoshi
Y
Y
Wanikawa
K
K
Ohga
A
A
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D006221:Halothane / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008305:Malignant Hyperthermia / Q000378:metabolism / Q000662:veterinary*; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013552:Swine; D013553:Swine Diseases / Q000378:metabolism*
C005147:5'-adenylyl (beta,gamma-methylene)diphosphonate; D002110:Caffeine; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D002118:Calcium; D006221:Halothane