Advancing age alters intracellular calcium buffering in rat adrenergic nerves

There is a marked increase with advancing age of stimulation-evoked neurotransmitter 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 alteration in neuronal and extraneuronal uptake of norepinephrine or a decline in feedback inhibition of release by prejunctional alpha2-adrenergic receptors. Measurement of intracellular calcium in fura-2-labeled superior cervical ganglion cells revealed elevated K+-evoked calcium transients in old compared to young neurons. Blockade of mitochondrial calcium uptake with dinitrophenol resulted in increased calcium transients in old neurons only. Furthermore, following blockade of mitochondrial calcium uptake the rate of return of calcium to resting levels was reduced to a greater degree in old cells as compared to young cells. The effects of dinitrophenol in old cells were attenuated when extracellular calcium was reduced. These findings suggest that older cells are more dependent on mitochondrial calcium buffering, perhaps due to changes in ATP dependent calcium uptake. Increased calcium transients as a result of altered intracellular calcium buffering offer a reasonable explanation for our previous observation of increased stimulation evoked norepinephrine release.