Denervation-induced decrease in mitochondrial calcium transport in rat hippocampus.

Abstract

Calcium accumulation by mitochondria and the activity and in vitro phosphorylation of pyruvate dehydrogenase were measured in control and partially denervated hippocampus. Calcium uptake was measured with a calcium-sensitive electrode and 45Ca2+ accumulation; both methods indicated that lesions of the entorhinal cortex produced a sizable reduction of calcium transport when mitochondria were fueled with pyruvate while much smaller changes were observed using succinate or ATP as energy sources. The decrease in calcium transport was evident by 24 hr after the lesion and was still present 6 months later. Synaptic and nonsynaptic mitochondria were similarly affected by the lesions. The activity and in vitro phosphorylation of pyruvate dehydrogenase were also significantly reduced following lesions of the entorhinal cortex, suggesting that denervation altered the endogenous state of phosphorylation of the mitochondrial enzyme. Commissural lesions but not septal lesions also resulted in a decrease in mitochondrial calcium transport when mitochondria were fueled with pyruvate. These findings suggest that denervation disturbs mitochondrial regulation of free calcium via an action on enzymes which regulate pyruvate dehydrogenase phosphorylation and activity. The potential relationship of this effect to degenerative changes associated with deafferentation and certain disease states is discussed.