PARTIAL RECOVERY OF SKELETAL-MUSCLE SODIUM-CHANNEL PROPERTIES IN AGEDRATS CHRONICALLY TREATED WITH GROWTH-HORMONE OR THE GH-SECRETAGOGUE HEXARELIN

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-gat ed sodium channels of skeletal muscle undergo during aging, by means o f the patch-clamp technique applied to fast-twitch muscle fibers. Two phenotypes of aged-rat fibers could be discriminated on the basis of c hannel conductance. In the young phenotype, sodium channels present a conductance of 18 pS as in young-adult rats. In the aged phenotype, ch annels present a conductance of 9 pS while ensemble average currents a ctivate and inactivate more slowly. Nevertheless, in all situations, s odium channels shared a number of biophysical properties, such as open probability, mean open time, steady-state inactivation and use-depend ent inhibition. Furthermore, channel density on extrajunctional sarcol emma was higher in aged rats, a result independent of the phenotype. C hronic treatment of aged rats with either GH or hexarelin restored cur rent kinetics but not channel conductance and density. These results c onfirm the specific age-related changes in sodium channel behavior and show that treatment with either GH or hexarelin has partial restorati ve effects. Moreover, hexarelin restored the firing capacity of fast-t witch muscle fibers, as did GH in previous studies. These findings sup port the possible therapeutic value of the synthetic peptide in cases of GH deficiency, as in the elderly.