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 microM) 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.

Increased calcium influx through acetylcholine receptors in dunce neurons.

Calcium homeostasis was studied in dunce, a Drosophila mutant that is defective in learning and memory. Fura 2-AM fluorescence photometry was used to measure the intracellular calcium concentration in wild type and dunce cleavage-arrested neurons under resting conditions and in response to neurotransmitters. After acetylcholine application, the peak [Ca2+]i was greater in dunce (693 +/- 125 nM) than in wild type neurons (464 +/- 154 nM), but half decay time was shorter in dunce (66 +/- 15 s) than in wild type neurons (104 +/- 40 s). In contrast, the application of glutamate, NMDA, dopamine, and serotonin had no effect on [Ca2+]i. These results indicate that calcium influx through acetylcholine receptors is increased in dunce, compared to wild type neurons. The results also suggest that calcium extrusion to the outside and/or calcium buffering are enhanced in dunce, compared to wild type neurons. This disturbance in the homeostasis of cytosolic calcium concentration in dunce may be implicated in defective associative learning in Drosophila, and may play a role in acute and chronic neurodegenerative disorders in the mammalian brain.

Drug effects on calcium homeostasis in mouse CA1 hippocampal neurons.

Voltage-dependent Ca2+ channels (VDCC) are important in control of neuronal excitability, synaptic transmission, and many other cellular process. Even the slightest alteration in Ca2+ currents can have a considerable impact on the neuronal function. However, it is still unknown whether Ca2+ currents are affected by neurotoxic drugs such as lead, cobalt, zinc, cadmium, thallium, lanthanum, and aluminum. We have characterized the effects of neurotoxic drugs on Ca2+ homeostasis in CA1 hippocampal C57BL mice. Fura 2-AM fluorescence photometry was used to measure intracellular Ca2+ concentration ([Ca2+]i) in the presence and absence of neurotoxic drugs (10 microM) in response to KCl application. The peak [Ca2+]i due to KCl application was reduced in the presence of lead (60%), cobalt (35%), zinc (62%), cadmium (71%), thallium (27%), and lanthanum (66%). By contrast, in the presence of aluminum the peak [Ca2+]i was either increased (46%) or it was not affected. These results indicate that neurotoxic drugs could block the entry of calcium into CA1 neurons via VDCC.