ADVANCING AGE ALTERS INTRACELLULAR CALCIUM BUFFERING IN RAT ADRENERGIC-NERVES

There is a marked increase with advancing age of stimulation-evoked ne urotransmitter release from vascular adrenergic nerves in the rat, an effect correlated with increased levels of plasma norepinephrine. This increase in norepinephrine release could not be accounted for by an a lteration in neuronal and extraneuronal uptake of norepinephrine or a decline in feedback inhibition of release by prejunctional alpha(2)-ad renergic receptors. Measurement of intracellular calcium in fura-2-lab eled superior cervical ganglion cells revealed elevated K+-evoked calc ium transients in old compared to young neurons. Blockade of mitochond rial calcium uptake with dinitrophenol resulted in increased calcium t ransients in old neurons only. Furthermore, following blockade of mito chondrial calcium uptake the rate of return of calcium to resting leve ls was reduced to a greater degree in old cells as compared to young c ells. The effects of dinitrophenol in old cells were attenuated when e xtracellular calcium was reduced. These findings suggest that older ce lls are more dependent on mitochondrial calcium buffering, perhaps due to changes in ATP dependent calcium uptake. Increased calcium transie nts as a result of altered intracellular calcium buffering offer a rea sonable explanation for our previous observation of increased stimulat ion evoked norepinephrine release. Copyright (C) 1996 Elsevier Science Inc.