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

J Physiol. 1999 Apr 15;516 ( Pt 2)(Pt 2):331-41. doi: 10.1111/j.1469-7793.1999.0331v.x.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium Channels / biosynthesis*
  • Calcium Channels / genetics*
  • Calcium Channels, L-Type
  • Electric Stimulation
  • Electrophysiology
  • Gene Expression Regulation / drug effects*
  • Insulin-Like Growth Factor I / pharmacology*
  • Isradipine / pharmacology
  • Membrane Potentials / physiology
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism*
  • Patch-Clamp Techniques
  • RNA, Antisense
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Calcium Channels
  • Calcium Channels, L-Type
  • RNA, Antisense
  • RNA, Messenger
  • Insulin-Like Growth Factor I
  • Isradipine