AGE-ASSOCIATED CHANGES OF CYTOPLASMIC CALCIUM HOMEOSTASIS IN CEREBELLAR GRANULE NEURONS IN-SITU - INVESTIGATION ON THIN CEREBELLAR SLICES

Mechanisms of cytoplasmic calcium homeostasis were investigated in adu lt and old CBA mice. The cytoplasmic calcium concentration ([Ca2+](i)) was measured on fura-2/AM loaded granule neurons in acutely isolated cerebellar slices. The resting [Ca2+](i) was significantly higher in s enile cerebellar granule neurons, being on average 60 +/- 15 nM (n = 1 63) in adult and 107 +/- 12 nM (n = 129) in old neurons. The depolariz ation-induced [Ca2+](i) transients were markedly altered in old neuron s as compared with adult ones: their amplitude was smaller by about fi ve times, the rate of rise was prolonged about two times, and the comp lete recovery to the resting level after the end of depolarization was about five times longer. The amplitude of calcium release from caffei ne/Ca2+-sensitive endoplasmic reticulum calcium stores also become sig nificantly smaller in old neurons (the amplitudes of [Ca]i transients evoked by 30 mM caffeine were 75 +/- 27 nM (n = 29) in adult and 25 +/ - 10 nM (n = 23) in old neurons). We conclude that neuronal aging is a ssociated with prominent changes in the mechanisms responsible for [Ca 2+](i) regulation. These changes presumably include lowering of voltag e-gated plasmalemmal Ca2+ influx and slowing down of Ca2+ extrusion fr om the cytoplasm.