Calcium homeostasis and mitochondrial oxidative metabolism interact closely in brain and both processes are impaired during hypoxia. Since the regulation of the pyruvate dehydrogenase complex (PDHC) may link these two processes, the relation of cytosolic free calcium (Ca2+i) to the activation state of PDHC (PDHa) was assessed in isolated nerve terminals (i.e. synaptosomes) under conditions that alter Ca2+i. K+depolarization elevated Ca2+iand PDHaand both responses required external calcium. Treatment with KCN, an in vitro model of hypoxia decreased ATP and elevated Ca2+iand PDHa. Furthermore, in the presence of KCN, PDHabecame more sensitive to K+depolarization as indicated by larger changes in PDHathan in Ca2+i. The calcium ionophore Br-A23187 elevated Ca2+i, but did not affect PDHa. K+depolarization elevated Ca2+iand PDHaeven if Ca2+iwas elevated by prior addition of ionophore or KCN. Previous in vivo studies by others show that PDHais altered during and after ischemia. The current in vitro results suggest that hypoxia, only one component of ischemia, is sufficient to increase PDHa. These data also further support the notion that PDHais regulated by Ca2+ias well as by other factors such as ATP. Our results are consistent with the concept that PDHain nerve endings may be affected by Ca2+iand that these two processes are clearly linked.
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