Thermal inactivation of the calcium regulatory mechanism of human skeletal muscle actomyosin: a possible contributing factor in the rigidity of malignant hyperthermia.
The muscular rigidity associated with anesthetically induced malignant hyperthermia has been attributed to an increase in myoplasmic free calcium concentration. However, previous in-vitro studies have shown that increased temperature can eliminate the calcium requirement for actin-myosin interaction. Therefore, the calcium dependency of human skeletal muscle actomyosin in response to temperature increases of the magnitude encountered in human muscle during hyperthermic episodes was investigated. Calcium dependency is expressed in terms of the ability of a calcium-chelating agent, EGTA, to inhibit the ATP-induced turbidity increase of actomyosin suspensions (superprecipitation). In the presence of millimolar concentrations of ATP and magnesium, EGTA completely inhibits superprecipitation at temperatures as high as 35 C. With further increase in temperature this inhibition is progressively reduced until, at 45 C, the extent of superprecipitation is independent of the calcium concentration. Loss of calcium control is potentiated by reduction in the ATP concentration. Since the muscular rigidity of malignant hyperthermia is associated with both an elevation of muscle temperature and a decline in muscle ATP content, it is evident that in this disorder conditions might exist for an increase in muscle tension that is independent of changes in intracellular free calcium concentration.
D000205:Actomyosin / Q000302:isolation & purification / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002122:Calcium Chloride / Q000494:pharmacology; D011232:Chemical Precipitation; D004533:Egtazic Acid / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008305:Malignant Hyperthermia / Q000378:metabolism*; D009127:Muscle Rigidity / Q000378:metabolism*; D013053:Spectrophotometry; D013696:Temperature
D004533:Egtazic Acid; D000255:Adenosine Triphosphate; D000205:Actomyosin; D008274:Magnesium; D002122:Calcium Chloride; D002118:Calcium