Adrenergic nerves compensate for a decline in calcium buffering during ageing

1 The ubiquitous involvement of intracellular calcium ([Ca2+](i)) in multip le neuronal pathways has led investigators to suggest that dysfunction of c alcium homeostasis may be the primary mediator of age-related neuronal dege neration. Recently, it was shown that sympathetic neurones from superior ce rvical ganglion (SCG) of aged rats demonstrate decreased sarco-/endoplasmic reticulum Ca2+-ATPase (SERCA)function and that aged neurones are more depe ndent upon mitochondria to control K+-evoked [Ca2+](i) transients. 2 Therefore, in the present study we investigated age-related changes in AT P-dependent calcium pumps of plasma membrane Ca2+-ATPase (PMCA) and SERCA i n acutely dissociated SCG cells from Fischer-344 rats aged 6 and 20 months. To distinguish between PMCA and SERCA pump activity, we applied the Ca2+-A TPase blocker vanadate and measured rates of recovery of K+-evoked [Ca2+]i transients by fura-2 microfluorometry. 3 Young SCG cells showed a biphasic response to vanadate over the vanadate concentration range (0.01-100 muM); however, old SCG cells showed only a si ngle response over the same concentration range. Additionally, old SCG cell s showed a greater sensitivity to Ca2+-ATPase blockade by vanadate. 4 The contribution of mitochondrial calcium uptake to regulate [Ca2+]i was also investigated. To measure the impact of mitochondrial calcium uptake, P MCAs and SERCAs were blocked with vanadate (100 muM) and extracellular sodi um was replaced with tetraethylammonium (TEA) to block Na+/Ca2+-exchange. T reated SCG cells showed a decline of 50% in rate of recovery of [Ca2+]i in both 6- and 20-month-old cells; however, this effect did not vary with age. 5 These data suggest that there is an age-related decline in function of SE RCAs, with an increased reliance on PMCAs to control high K+-evoked [Ca2+]i transients. In addition, there appears to be no age-related change in the capacity of the mitochondria to restore [Ca2+]i transients to basal levels.