SERCA function declines with age in adrenergic nerves from the superior cervical ganglion

1 Intracellular calcium is a universal second messenger integrating numerou s cellular pathways. An age-related breakdown in the mechanisms controlling [Ca2+](i) homeostasis could contribute to neuronal degeneration. One compo nent of neuronal calcium regulation believed to decline with age is the fun ction of sarco/endoplasmic reticulum calcium ATPase (SERCA) pumps. 2 Therefore we investigated the impact of age on the capacity of SERCA pump s to control high (68 mM) [K+]-evoked [Ca2+](i)-transients in acutely disso ciated superior cervical ganglion (SCG) cells from 6- and 20-month-old Fish er-344 rats. Calcium transients were measured by fura-2 microfluorometry in the presence of vanadate (0.1 muM) to selectively block plasma membrane ca lcium ATPase (PMCA) pumps, dinitrophenol (100 muM) to block mitochondrial c alcium uptake and extracellular sodium replaced with tetraethylammonium to block Na+/ Ca2+-exchanger, thus forcing the neuronal cells to rely on SERCA uptake to control [Ca2+](i) homeostasis. 3 In the presence of these calcium buffering blockers, the rate of recovery of [Ca2+](i) was significantly slower and time to recover to approximately 90% of resting [Ca2+](i) was significantly greater in SCG cells from old ( 20 months) compared with young (6 months) animals. 4 This age-related change in the recovery phase of [K+]-evoked [Ca2+](i)-tr ansients could not be explained by differences in the sensitivity of SCG ce lls to the calcium buffering blockers, as no age-related difference in basa l [Ca2+](i) was observed. 5 These studies illustrate that when rat SCG cells are forced to rely on SE RCAs to buffer [K+]- evoked [Ca2+](i)-transients, an age-related decline in SERCA function is revealed. Such age-related declines in calcium regulatio n coupled with neuronal sensitivity to calcium overload underscore the impo rtance of understanding the components of [Ca2+](i) homeostasis and the fun ctional compensation that may occur with advancing age.