Age-associated changes of cytoplasmic calcium homeostasis in cerebellar granule neurons in situ: investigation on thin cerebellar slices

Abstract

Mechanisms of cytoplasmic calcium homeostasis were investigated in adult 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 senile cerebellar granule neurons, being on average 60 +/- 15 nM (n = 163) in adult and 107 +/- 12 nM (n = 129) in old neurons. The depolarization-induced [Ca2+]i transients were markedly altered in old neurons as compared with adult ones: their amplitude was smaller by about five times, the rate of rise was prolonged about two times, and the complete recovery to the resting level after the end of depolarization was about five times longer. The amplitude of calcium release from caffeine/Ca(2+)-sensitive endoplasmic reticulum calcium stores also become significantly smaller in old neurons (the amplitudes of [Ca2+]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 associated with prominent changes in the mechanisms responsible for [Ca2+]i regulation. These changes presumably include lowering of voltage-gated plasmalemmal Ca2+ influx and slowing down of Ca2+ extrusion from the cytoplasm.