Partial recovery of skeletal muscle sodium channel properties in aged rats chronically treated with growth hormone or the GH-secretagogue hexarelin

J Pharmacol Exp Ther. 1998 Aug;286(2):903-12.

Abstract

This study was aimed at investigating the effects of chronic treatment of aged rats with growth hormone (GH, 8 weeks) or the GH-secretagogue hexarelin (4 weeks) on the biophysical modifications that voltage-gated sodium channels of skeletal muscle undergo during aging, by means of the patch-clamp technique applied to fast-twitch muscle fibers. Two phenotypes of aged-rat fibers could be discriminated on the basis of channel conductance. In the young phenotype, sodium channels present a conductance of 18 pS as in young-adult rats. In the aged phenotype, channels present a conductance of 9 pS while ensemble average currents activate and inactivate more slowly. Nevertheless, in all situations, sodium channels shared a number of biophysical properties, such as open probability, mean open time, steady-state inactivation and use-dependent inhibition. Furthermore, channel density on extrajunctional sarcolemma was higher in aged rats, a result independent of the phenotype. Chronic treatment of aged rats with either GH or hexarelin restored current kinetics but not channel conductance and density. These results confirm the specific age-related changes in sodium channel behavior and show that treatment with either GH or hexarelin has partial restorative effects. Moreover, hexarelin restored the firing capacity of fast-twitch muscle fibers, as did GH in previous studies. These findings support the possible therapeutic value of the synthetic peptide in cases of GH deficiency, as in the elderly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Animals
  • Electrophysiology
  • Growth Hormone / metabolism*
  • Ion Channel Gating / drug effects
  • Male
  • Muscle Fibers, Skeletal / drug effects
  • Muscle Fibers, Skeletal / metabolism
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism*
  • Oligopeptides / pharmacology*
  • Patch-Clamp Techniques
  • Rats
  • Rats, Wistar
  • Sodium Channels / drug effects
  • Sodium Channels / metabolism*

Substances

  • Oligopeptides
  • Sodium Channels
  • hexarelin
  • Growth Hormone