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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.

To evaluate the effect of long-term exposure to heavy metals on skeletal muscle, chronic subcutaneous injections for 7 days of two level treatments (low dose, 0.1 mg/kg and high dose, 1 mg/kg) of lead acetate were investigated. Comparative analyses of in situ dorsiflexor muscle isometric contractile characteristics were studied in urethane-anesthetized (2 mg/g, i.p.) control and lead-exposed male mice. Control muscle-twitch tension reached an average of 1.81 +/- 0.06 g. Chronic lead (Pb2+) treatments did not affect muscle contractile speed, but reduced significantly the twitch tension in both high and low doses when compared to control animals. This effect was in a dose-dependent manner; 1.21 +/- 0.07 g for low dose and 0.90 +/- 0.05 g for high dose. These chronic Pb2+ treatments accelerated muscle fatigue after 250 stimuli (25 Hz for 10 sec) in both the low and high doses equally. However, marked elevation in tetanic (25 Hz) specific tension were observed in the high-dose, chronically treated animals, indicating some changes in contractile apparatus function. The high dose of chronic Pb2+ treatment induced ultrastructural changes, including reduced number of synaptic vesicles, disruption of mitochondria and increased number of smooth endoplasmic reticulum and myelin-like figures in the intramuscular axons and neuromuscular junctions. Chronic Pb2+ treatment caused extensive disruption of the sarcoplasmic mitochondria and increased the number of myelin-like figures in the muscle. These results suggest that exposure to Pb2+ at a low concentration can compromise the in situ skeletal muscle isometric contraction.

To evaluate the effect of partial denervation on age changes, morphological and physiological parameters were studied in young versus old extensor digitorum longus (EDL) muscles. The aims of this study were to elucidate synaptic maintenance in general and specifically to assess the adaptability of motor neurons from young and old animals to an enlarged field of innervation. Partial denervation was carried out in two groups of 30-40 g mice, aged within 6 or 24 months, by sectioning of the nerve supplying EDL muscle under methoxyfluorane anaesthesia. Sham operations were carried out on additional animals which served as controls. Five weeks' post-surgery, the safety factor of synaptic transmission was estimated by dividing the nerve-evoked twitch tension generated in 1 mM Ca2+ Krebs by that generated in 2.5 mM Ca2+ Krebs. Low Ca2+ Krebs caused a more pronounced decline in twitch tension in young control EDL muscles than old control. After partial denervation, young EDL twitch tensions were not significantly different while old were 20% of those in normal Krebs. Zinc Iodide Osmium (ZIO) stained nerve terminal parameters were significantly increased with aging. After partial denervation, nerve terminal areas were 46 and 39% larger in young and old mice, respectively, compared to their corresponding controls. Present data suggest that motor neurons of old mice are unable to develop and maintain an enlarged field of innervation.

To determine whether increased transmitter release from soleus nerve terminals of old C57BL/6J mice is caused by an altered Ca2+ regulation, the time course of post-tetanic potentiation of miniature endplate potential (MEPP) frequency was used as an indicator of the kinetics of Ca2+ metabolism in young (10 months) and old (24 months) mice. Post-tetanic potentiation properties were studied in either (1) 0.2 mM Ca2+, 5.0 mM Mg2+ Krebs; or (2) Ca2(+)-free/EGTA Krebs to eliminate Ca2+ influx, and thereby isolated Ca2+ buffering. In the 0.2 mM Ca2+ Krebs, the time constants of decay of augmentation (TA) and potentiation (TP) were longer in old (TA = 10.3 +/- 1.0 sec, TP = 195.3 +/- 5.4 sec) than in young (TA = 7.0 +/- 0.7 sec, TP = 78.8 +/- 6.6 sec) nerve terminals. Evoked transmitter release was measured in 0.4 mM Ca2+, 2.75 mM Mg2+ Krebs. Quantal content of the endplate potential was positively correlated with TA (r = 0.95) and with TP (r = 0.98). In the Ca2(+)-free/EGTA Krebs, there was no difference in post-tetanic potentiation properties between young and old terminals. These results suggest that Ca2+ influx into the soleus nerve terminal increases with aging. This may explain, at least in part, the increased quantal content observed at old terminals.