Role of sarcolemmal changes in cardiac pathophysiology.
Sarcolemmal Ca++-ATPase, Mg++-ATPase, and (Na+-K+)-ATPase activities were increased in late stages of heart failure in myopathic hamsters (BIO 14.6) without any changes in the adenylate cyclase activity. On the other hand, these hamsters at early and moderate stages of heart failure showed depressions in mitochondrial calcium binding and uptake and microsomal calcium binding. Sarcolemmal (Na+-K+)-ATPase was decreased in failing hearts because of substrate lack, oxygen lack, and perfusion with Ca++-free, Na+-free, or K+-free medium. Both Mg++-ATPase and Ca++-ATPase activities of sarcolemma did not change on perfusing the hearts with substrate-free, hypoxic, Na+-free, or K+-free medium. Adenylate cyclase activity decreased on substrate-free or Ca++-free perfusion. Intracellular calcium overload produced by perfusing the hearts with medium containing calcium after Ca++-free perfusion was associated with decrease in all the sarcolemmal-bound enzyme activities. All types of failing hearts employed in this study showed a dramatic shift in the electrolyte composition. Failure of the cardiac muscle to generate contractile force on treatment with trypsin was associated with defects in the functions of sarcolemma, mitochondria, and sarcoplasmic reticulum, whereas such an effect on treatment with phospholipase C was limited to alterations in the activities of sarcolemma. The data suggest that abnormality at the level of sarcolemma plays an important role in the pathogenesis of heart dysfunction; however, the degree and direction of alterations in the sarcolemmal functions seem to be dependent upon the type of heart failure.
D000200:Action Potentials; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000375:Aging; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002415:Cats; D006224:Cricetinae; D004195:Disease Models, Animal; D004285:Dogs; D004789:Enzyme Activation / Q000187:drug effects; D006321:Heart / Q000503:physiopathology*; D006333:Heart Failure / Q000201:enzymology / Q000503:physiopathology*; D008274:Magnesium / Q000494:pharmacology; D008861:Microsomes / Q000378:metabolism; D008931:Mitochondria, Muscle / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D012508:Sarcolemma / Q000201:enzymology / Q000502:physiology* / Q000648:ultrastructure; D012964:Sodium / Q000494:pharmacology
D012964:Sodium; D000251:Adenosine Triphosphatases; D008274:Magnesium; D011188:Potassium; D002118:Calcium