Global ischemia increases the density of voltage-dependent calcium channels in porcine cardiac sarcolemma.
The objective of this work was to determine whether normothermic global cardiac ischemia in a porcine model was associated with a change in the density (Bmax) of voltage-dependent calcium channels in myocardial sarcolemmal membranes. Pigs were anesthetized, a thoracotomy was performed, and samples were taken of the left and right ventricles from control and ischemic hearts. Dihydropyridine-binding sites were quantified using [3H]isradipine, and 5'-nucleotidase activity was measured by the liberation of inorganic phosphate from adenosine monophosphate. Bmax and dissociation constants and 5'-nucleotidase activity for control and ischemic tissues, respectively, were compared by using Student's t-test for unpaired samples. After normothermic global ischemia, the Bmax of [3H]isradipine binding increased in the left ventricle by 81% (299% +/- 1.7% to 540% +/- 11% fmoles/mg, P < 0.01) and in the right ventricle by 33% (387% +/- 9.9% to 515% +/- 38% fmoles/mg, P < 0.01) compared with control. 5'-nucleotidase activity increased by 48% in the left ventricle and by 96% in the right ventricle (p < 0.05). Fifteen minutes of normothermic ischemia in the pig is associated with marked sarcolemmal abnormalities, including increases in specific dihydropyridine binding and 5'-nucleotidase activity, which reflect global changes in membrane function, which might contribute to the increase in myoplasmic calcium during ischemia.
Blanck
T J
TJ
Department of Anesthesiology, Hospital for Special Surgery, New York, New York 10021, USA.
Yasukochi
S
S
Quigg
M
M
Curtis
W E
WE
Gardner
T J
TJ
D015720:5'-Nucleotidase / Q000378:metabolism; D000818:Animals; D002121:Calcium Channel Blockers / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D004095:Dihydropyridines / Q000378:metabolism; D006352:Heart Ventricles / Q000201:enzymology; D066298:In Vitro Techniques; D017275:Isradipine / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D012508:Sarcolemma / Q000378:metabolism*; D013552:Swine
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; C038806:1,4-dihydropyridine; D015720:5'-Nucleotidase; D017275:Isradipine