AGING AND ALCOHOL ON NEURONAL CALCIUM METABOLISM

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The overall aim of this project is to characterize the relationships between aging, acute and chronic ethanol administration and altered neuronal calcium transport and calcium-dependent stimulus-secretion coupling. Our general hypothesis is that both ethanol administration and aging result in a reduction in calcium entry through calcium channels into neurons and a change in calcium metabolism in the neuronal cytosol. In combination, ethanol and aging may facilitate the occurrence of decrements in calcium channel function and exacerbate the changes in intracellular calcium homeostasis. Studies are designed to characterize the influence of acute and chronic alcohol on the kinetics of voltage-dependent calcium channels in synaptosomes and synaptoneurosomes isolated from young versus old male, Fischer 344 rats. Experiments will be conducted in seven brain regions(cerebral cortex, cerebellum, brain stem, midbrain, hypothalamus, hippocampus and striatum) known to vary in sensitivity to aging and alcohol. these experiments will examine simultaneously (and in the sam samples as the calcium experiments) endogenous dopamine and norepinephrine release to examine the influence of ethanol and aging on stimulus-secretion coupling processes. Studies will be conducted to determine the effects of age and acute and chronic alcohol on dihydropyridine-sensitive calcium channels in brain regional synaptosomes and synaptoneurosomes. The brain regions to be studied will be the same seven as described above. These brain regions differ in the distribution of dihdropyridine binding sites. Finally, studies will be conducted to characterize the effects of acute and chronic ethanol administration on free, cytosolic calcium concentration of synaptosomes and synaptoneurosomes in young versus old rats. These studies will be conducted on the seven brain regions described above using the intracellular calcium indicator Fura-2.