Responses of Electrical Activity and Redox State of Cytochrome Oxidase to Oxygen Insufficiency in Perfused Rat Brain In Situ
During the transition from normoxia to hypoxia in brain tissue, the energy related metabolites remain unchanged until the cerebral oxygen consumption decreases. For example, ATP levels are kept normal at arterial oxygen tensions higher than around 25 mmHg. Below this, ATP begins to decrease together with the increases of ADP and AMP, where oxygen consumption decreases. The electrical activity is also attenuated. The activation of glycolytic flux prevents, in part, the decline of ATP (Sylvia and Piantadosi, 1988, Erecinska and Silver, 1989). In addition, it has been reported that neuronal activity is suppressed prior to decreases in ATP. Thus, the energy failure is not solely responsible for suppression of brain function in hypoxic conditions. Previously, we have calibrated the oxygen dependence of the redox centers of cytochrome oxidase, heme aa3 and copper, in isolated mitochondria (Hoshi et al., 1993). The redox state of heme aa3 depends on both the energy state and the respiratory rate, whereas the redox state of copper is independent of both the energy state and the respiratory rate. Thus, simultaneous measurements of these chromophores in cytochrome oxidase can give both oxygen concentration and energy state at mitochondria. On the basis of the in vitro data of isolated mitochondria, we measured the redox state of cytochrome oxidase and the electrical activity in perfused rat brain in situ. The relationship between functional failure and oxygen insufficiency became much clearer from the present study, which is presented here.
KeywordsRedox State Hypoxic Condition Cytochrome Oxidase Oxygen Insufficiency Perfuse Brain
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- Hoshi, Y., Hazeki, O., and Tamura, M., 1993, Oxygen dependence of redox state of copper in cytochrome oxidase in vitro, J. Appi. Physiol. 74: 1622–1627.Google Scholar