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Biophys J, March 2002, p. 1338-1344, Vol. 82, No. 3

Sustained Overexpression of IGF-1 Prevents Age-Dependent Decrease in Charge Movement and Intracellular Ca2+ in Mouse Skeletal Muscle

Zhong-Min Wang,* María Laura Messi,* and Osvaldo Delbono*dagger

From the Departments of  *Physiology and Pharmacology and  dagger Internal Medicine, Gerontology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157 USA

In this work we tested the hypothesis that transgenic sustained overexpression of IGF-1 prevents age-dependent decreases in charge movement and intracellular Ca2+ in skeletal muscle fibers. To this end, short flexor digitorum brevis (FDB) muscle fibers from 5-7- and 21-24-month-old FVB (wild-type) and S1S2 (IGF-1 transgenic) mice were studied. Fibers were voltage-clamped in the whole-cell configuration of the patch-clamp technique according to described procedures (Wang, Z. M., M. L. Messi, and O. Delbono. 1999. Biophys. J. 77:2709-2716). Charge movement and intracellular Ca2+ concentration were recorded simultaneously. The maximum charge movement (Qmax) recorded in young wild-type and transgenic mice was (mean ± SEM, in nC µF-1): 52 ± 2.1 (n = 46) and 54 ± 1.9 (n = 38) (non-significant, ns), respectively, whereas in old wild-type and old transgenic mice the values were 36 ± 2.1 (n = 32) and 49 ± 2.3 (n = 35), respectively (p < 0.01). The peak intracellular calcium [Ca2+]i recorded in young wild-type and transgenic mice was (in µM): 14.5 ± 0.9 and 16 ± 2.1 (ns), whereas in old wild-type and transgenic mice the values were 9.9 ± 0.1 and 14 ± 1.1 (p < 0.01), respectively. No significant changes in the voltage distribution or steepness of the Q-V or [Ca2+]-V relationship were found. These data support the concept that overexpression of IGF-1 in skeletal muscle prevents age-dependent reduction in charge movement and peak [Ca2+]i.

Biophys J, March 2002, p. 1338-1344, Vol. 82, No. 3
© 2002 by the Biophysical Society   0006-3495/02/03/1338/07  $2.00


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