Partial recovery of skeletal muscle sodium channel properties in aged rats 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-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.
Desaphy
J F
JF
Unit of Pharmacology, Department of Pharmacobiology, Faculty of Pharmacy, University of Bari, Bari, Italy.
De Luca
A
A
Pierno
S
S
Imbrici
P
P
Camerino
D C
DC
D000375:Aging / Q000378:metabolism*; D000818:Animals; D004594:Electrophysiology; D013006:Growth Hormone / Q000378:metabolism*; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*
D009842:Oligopeptides; D015222:Sodium Channels; C086184:hexarelin; D013006:Growth Hormone