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

We investigated whether insulin-like growth factor-1 (IGF-1), an endogenous potent activator of skeletal muscle proliferation and differentiation, enhances L-type Ca 2+ channel gene expression resulting in increased functional voltage sensors in single skeletal muscle cells. Charge movement and inward Ca 2+ current were recorded in primary cultured rat myoballs using the whole-cell configuration of the patch-clamp technique. Ca 2+ current and maximum charge movement ( Q max ) were potentiated in cells treated with IGF-1 without significant changes in their voltage dependence. Peak Ca 2+ 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 Q max was 12·9 ± 0·4 and 22·0 ± 0·3 nC μF −1 , respectively ( P < 0·01). The number of L-type Ca 2+ channels was found to increase in the same preparation. The maximum binding capacity ( B max ) of the high-affinity radioligand [ 3 H]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 [ 3 H]PN200-110 was found. Antisense RNA amplification showed a significant increase in the level of mRNA encoding the L-type Ca 2+ channel α1-subunit in IGF-1-treated cells. This study demonstrates that IGF-1 regulates charge movement and the level of L-type Ca 2+ channel α1-subunits through activation of gene expression in skeletal muscle cells.