Ischemia induces a specific, reversible, time- and temperature-dependent reduction in the density of dihydropyridine binding sites in rat hearts.
The time course of normothermic (37 degrees C) and hypothermic (22 degrees C) global ischemia, and of post-ischemic reperfusion on the affinity (KD), selectivity, and density (Bmax) of the high-affinity 1,4 dihydropyridine (DHP) calcium channel antagonist binding sites were studied in isolated rat heart membranes, using (+)3HPN 200-110. Short periods (10 or 20 min) of ischemia at either 37 degrees C or 22 degrees C altered neither the KD nor Bmax of these binding sites as compared with aerobic controls. By contrast, longer periods of normothermic ischemia (30 or 60 min) caused a reduction (p less than 0.05) in Bmax (36% after 30 min and 32.7% after 60 min) without change of KD. This reduction in Bmax was reversed by 15-min reperfusion at 37 degrees C after 30 but not 60-min ischemia. There was no effect of ischemia (up to 60 min) on the density of DHP binding sites under hypothermic conditions. Irrespective of the experimental conditions the selectivity of the binding sites was maintained, with (+)PN 200-100 greater than (-)Bay K8644 greater than (-)PN 200-110 = (+)Bay K8644 much greater than (-)D600 in displacing (+)3HPN 200-110, and D-cis diltiazem stimulating the binding. These results show that the ischemia-induced change in Bmax is specific, reversible, and time- and temperature-dependent.
Gu et al. (1988) studied this question.