Regulation of excitation contraction coupling by insulin-like growth factor-1 in aging skeletal muscle.
Excitation-contraction (EC) uncoupling is a primary muscle alteration and constitutes a major cause of decline in skeletal muscle force with aging. The structural substratum for EC uncoupling in muscles from aging mammals is a reduction in number of dihydropyridine receptors (DHPR) at the T-tubule and SR membrane leading to an increase in the percent of sarcoplasmic reticulum calcium release channels or ryanodine receptors (RyR1) uncoupled to DHPR. The main functional consequence of this alteration is a failure in the transduction of sarcolemmal depolarization into a calcium signal and a mechanical response. This review summarizes recent studies from our laboratory aimed at elucidating the modulation of EC coupling by insulin-like growth factor-1 (IGF-1) in skeletal muscle. We demonstrated that transgenic overexpression of human IGF-1 exclusively in skeletal muscle increases the number and prevents age-related decline in the number of DHPR. IGF-1 enhances rat skeletal muscle DHPR function and gene expression. The functional significance of these findings is that IGF-1 prevents the age-related decline in muscle force.
Departments of Physiology and Pharmacology and Internal Medicine, Gerontology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA. odelbono@wfubmc.edu
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D000375:Aging / Q000502:physiology*; D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D009119:Muscle Contraction / Q000502:physiology*; D009124:Muscle Proteins / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology*; D009133:Muscular Atrophy / Q000517:prevention & control; D051381:Rats; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D020746:Calcium Channels, L-Type; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D007334:Insulin-Like Growth Factor I