GLOBAL-ISCHEMIA INCREASES THE DENSITY OF VOLTAGE-DEPENDENT CALCIUM CHANNELS IN PORCINE CARDIAC SARCOLEMMA

The objective of this work was to determine whether normothermic globa l cardiac ischemia in a porcine model was associated with a change in the density (B-max) of voltage-dependent calcium channels in myocardia l sarcolemmal membranes. Pigs were anesthetized, a thoracotomy was per formed, and samples were taken of the left and right ventricles from c ontrol and ischemic hearts. Dihydropyridine-binding sites were quantif ied using [H-3]isradipine, and 5'-nucleotidase activity was measured b y the liberation of inorganic phosphate from adenosine monophosphate. B-max and dissociation constants and 5'-nucleotidase activity for cont rol and ischemic tissues, respectively, were compared by using Student 's t-test for unpaired samples. After normothermic globalischemia, the B-max of [H-3]isradipine binding increased in the left ventricle by 8 1% (299% +/- 1.7% to 540% +/- 11% fmoles/mg, P < 0.01) and in the righ t ventricle by 33% (387% +/- 9.9% to 515% +/- 38% fmoles/mg, P < 0.01) compared with control. 5'-nucleotidase activity increased by 48% in t he left ventricle and by 96% in the right ventricle (p < 0.05). Fiftee n minutes of normothermic ischemia in the pig is associated with marke d sarcolemmal abnormalities, including increases in specific dihydropy ridine binding and 5'-nucleotidase activity, which reflect global chan ges in membrane function, which might contribute to the increase in my oplasmic calcium during ischemia.