The sarcolemmal Ca2+-ATPase of the ischemic-reperfused myocardium: protective effect of hypocalcemia on calmodulin-stimulated activity.
This study was designed to examine the role of calcium in the ischemia-induced changes of calmodulin-stimulated Ca2+-ATPase activity of heart sarcolemma of dogs subjected to coronary artery ligation (90 min) and reperfusion (30 min). This was attained by the application of systemic hemodialysis with low Ca2+ dialysate in six dogs (group A) and the comparison of the results with those obtained from animals subjected to normal Ca2+ hemodialysis (control group B, n=7). A very significant (p<0.001) decrease was found in the calmodulin-stimulated Ca2+-ATPase activity measured in the ischemic and non-ischemic parts of group B. This was associated with a decrease in the maximal velocity (v(max)) of the reaction of stimulation and an increase in the apparent Km for calmodulin. The kinetics of the calmodulin-stimulated Ca2+-ATPase also assessed in the presence of trifluoroperazine, a specific inhibitor for calmodulin binding, showed that the affinity for calmodulin was higher in the ischemic part of group A than of B, while v(max) was not substantially different. The above data may suggest that the inhibition of the calmodulin-stimulated Ca2+-ATPase produced by ischemia-reperfusion and its preservation under low Ca2+, are exerted at the calmodulin-binding site of the enzyme.
Samouilidou
E C
EC
Biochemical Research Laboratory, Alexandra State and University Hospital, Athens, Greece.
Karli
J N
JN
Levis
G M
GM
Darsinos
J T
JT
D000818:Animals; D000252:Calcium-Transporting ATPases / Q000187:drug effects* / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006321:Heart / Q000187:drug effects*; D006996:Hypocalcemia / Q000503:physiopathology*; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000201:enzymology; D012508:Sarcolemma / Q000187:drug effects / Q000201:enzymology*
D002147:Calmodulin; D000252:Calcium-Transporting ATPases