Modulation of neuronal [Ca²⁺]_i by caffeine is altered with aging

Voltage-dependent calcium channels play an important role in controlling many neuronal processes such as neuronal excitability and synaptic transmission. Any slight alteration in intracellular calcium concentration ([Ca²⁺]_i) can have a considerable impact on various neuronal functions. The effects of caffeine on [Ca²⁺]_i were studied in CA1 hippocampal neurons of young (2 months) and old (24 months) C57BL mice. Fura 2-AM fluorescence photometry was used to measure [Ca²⁺]_i in the presence and absence of caffeine (100 μM) in response to KCl (26 mM) application. Caffeine enhanced the peak [Ca²⁺]_i as compared to control solution in young mice (control: 325 ± 8 nM, caffeine: 402 ± 10 nM), but had no effect on the peak [Ca²⁺]_i in old mice (control: 222 ± 6 nM, caffeine: 223 ± 7 nM). These results indicate that caffeine can impact neuronal functions through the modification of [Ca²⁺]_i. The lack of caffeine-induced modulation of [Ca²⁺]_i in old mice suggests that this role of caffeine has been compromised with aging.