There is evidence that the complex process of sarcopenia in human aged skeletal muscle is linked to the modification of mechanisms controlling Ca(2+) homeostasis. To further clarify this issue, we assessed the changes in the kinetics of activation and inactivation of T- and L-type Ca(2+) currents in in vitro differentiated human myotubes, derived from satellite cells of healthy donors aged 2, 12, 76 and 86 years. The results showed an age-related decrease in the occurrence of T- and L-type currents. Moreover, significant age-dependent alterations were found in L-(but not T) type current density, and activation and inactivation kinetics, although an interesting alteration in the kinetics of T-current inactivation was observed. The T- and L-type Ca(2+) currents play a crucial role in regulating Ca(2+) entry during satellite cells differentiation and fusion into myotubes. Also, the L-type Ca(2+) channels underlie the skeletal muscle excitation-contraction coupling mechanism. Thus, our results support the hypothesis that the aging process could negatively affect the Ca(2+) homeostasis of these cells, by altering Ca(2+) entry through T- and L-type Ca(2+) channels, thereby putting a strain on the ability of human satellite cells to regenerate skeletal muscle in elderly people.
Calcium current kinetics in young and aged human cultured myotubes
LUIN, ELISA;LORENZON, Paola;RUZZIER, FABIO
2008-01-01
Abstract
There is evidence that the complex process of sarcopenia in human aged skeletal muscle is linked to the modification of mechanisms controlling Ca(2+) homeostasis. To further clarify this issue, we assessed the changes in the kinetics of activation and inactivation of T- and L-type Ca(2+) currents in in vitro differentiated human myotubes, derived from satellite cells of healthy donors aged 2, 12, 76 and 86 years. The results showed an age-related decrease in the occurrence of T- and L-type currents. Moreover, significant age-dependent alterations were found in L-(but not T) type current density, and activation and inactivation kinetics, although an interesting alteration in the kinetics of T-current inactivation was observed. The T- and L-type Ca(2+) currents play a crucial role in regulating Ca(2+) entry during satellite cells differentiation and fusion into myotubes. Also, the L-type Ca(2+) channels underlie the skeletal muscle excitation-contraction coupling mechanism. Thus, our results support the hypothesis that the aging process could negatively affect the Ca(2+) homeostasis of these cells, by altering Ca(2+) entry through T- and L-type Ca(2+) channels, thereby putting a strain on the ability of human satellite cells to regenerate skeletal muscle in elderly people.Pubblicazioni consigliate
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