CHANGES OF RESPIRATORY-CHAIN ACTIVITY IN MITOCHONDRIAL AND SYNAPTOSOMAL FRACTIONS-ISOLATED FROM THE GERBIL BRAIN AFTER GRADED ISCHEMIA

In this study we have examined (1) the integrated function of the mito chondrial respiratory chain by polarographic measurements and (2) the activities of the respiratory chain complexes I, II-III, and IV as wel l as the ATP synthase (complex V) in free mitochondria and synaptosome s isolated from gerbil brain, after a 30-min period of graded cerebral ischaemia. These data have been correlated with cerebral blood flow ( CBF) values as measured by the hydrogen clearance technique. Integrate d functioning of the mitochondrial respiratory chain, using both NAD-l inked and FAD-linked substrates, was initially affected at CBF values of similar to 35 ml 100 g(-1) min(-1), and declined further as the CBF was reduced. The individual mitochondrial respiratory chain complexes , however, showed differences in sensitivity to graded cerebral ischae mia. Complex I activities decreased sharply at blood flows below simil ar to 30 ml 100 g(-1) min(-1) (mitochondria and synaptosomes) and comp lex II-III activities decreased at blood flows below 20 ml 100 g(-1) m in(-1) (mitochondria) and 35-30 ml 100 g(-1) min(-1) (synaptosomes). A ctivities declined further as CBF was reduced below these levels. Comp lex V activity was significantly affected only when the blood flow was reduced below 15-10 ml 100 g(-1) min(-1) (mitochondria and synaptosom es). In contrast, complex IV activity was unaffected by graded cerebra l ischaemia, even at very low CBF levels.