Insulin-like growth factor-1 enhances rat skeletal muscle charge movement and L-type Ca2+ channel gene expression

1. We investigated whether insulin-like growth factor-1 (IGF-1), an endogenous potent activator of skeletal muscle proliferation and differentiation, enhances L-type Ca2+ channel gene expression resulting in increased functional voltage sensors in single skeletal muscle cells. 2. Charge movement and inward Ca2+ current were recorded in primary cultured rat myoballs using the whole-cell configuration of the patch-clamp technique. Ca2+ current and maximum charge movement (Qmax) were potentiated in cells treated with IGF-1 without significant changes in their voltage dependence. Peak Ca2+ current in control and IGF-1-treated cells was -7.8 +/- 0.44 and -10. 5 +/- 0.37 pA pF-1, respectively (P < 0.01), whilst Qmax was 12.9 +/- 0.4 and 22.0 +/- 0.3 nC microF-1, respectively (P < 0.01). 3. The number of L-type Ca2+ channels was found to increase in the same preparation. The maximum binding capacity (Bmax) of the high-affinity radioligand [3H]PN200-110 in control and IGF-1-treated cells was 1.21 +/- 0.25 and 3.15 +/- 0.5 pmol (mg protein)-1, respectively (P < 0.01). No significant change in the dissociation constant for [3H]PN200-110 was found. 4. Antisense RNA amplification showed a significant increase in the level of mRNA encoding the L-type Ca2+ channel alpha1-subunit in IGF-1-treated cells. 5. This study demonstrates that IGF-1 regulates charge movement and the level of L-type Ca2+ channel alpha1-subunits through activation of gene expression in skeletal muscle cells.