Chronic administration of taurine to aged rats improves the electrical and contractile properties of skeletal muscle fibers.
A reduction of resting chloride conductance (GCl) and a decrease of the voltage threshold for contraction are observed during aging in rat skeletal muscle. The above alterations are also observed in muscle of adult rat after taurine depletion. As lower levels of taurine were found by others in aged rats compared to young rats, we tested the hypothesis that a depletion of taurine may contribute to the alteration of the electrical and contractile properties we found in skeletal muscle during aging. This was accomplished by evaluating the potential benefit of a pharmacological treatment with the amino acid. To this aim 25-mo-old Wistar rats were chronically treated (2-3 mo) with taurine (1 g/kg p.o. daily) and the effects of such a treatment were evaluated in vitro on the passive and active membrane electrical properties of extensor digitorum longus muscle fibers by means of current-clamp intracellular microelectrode technique. Excitation-contraction coupling was also evaluated by measuring the voltage threshold for contraction with the intracellular microelectrode "point" voltage clamp method. In parallel muscle and blood taurine contents were determined by high-performance liquid chromatography. Taurine supplementation significantly raised taurine content in muscle toward that found in adult rats. Supplementation also significantly increased GCl vs. the adult value, in parallel the excitability characteristics (threshold current and latency) related to this parameter were ameliorated. The increase of GCl induced by taurine was accompanied by a restoration of the pharmacological sensitivity to the R(+) enantiomer of 2-(p-chlorophenoxy) propionic acid, a specific chloride channel ligand. In parallel also the protein kinase C-mediated modulation of the channel was restored; in fact the potency of 4-beta-phorbol 12, 13-dibutyrate in reducing GCl was lower in taurine-treated muscles vs. untreated aged, being rather similar to that observed in adult. The treatment also improved the mechanical threshold for contraction of striated fibers which in aged rats is shifted toward more negative potentials, moving it toward the adult values. Our results suggest that the reduction of taurine content could play a role in the alteration of electrical and contractile properties observed during aging. These findings may indicate a potential application of taurine in ensuring normal muscle function in the elderly.
Pierno
S
S
Unit of Pharmacology, Department of Pharmacobiology, Faculty of Pharmacy, University of Bari, Bari, Italy.
De Luca
A
A
Camerino
C
C
Huxtable
R J
RJ
Camerino
D C
DC
D000375:Aging / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D018118:Chloride Channels / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000502:physiology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D013654:Taurine / Q000032:analysis / Q000494:pharmacology*
D018118:Chloride Channels; D013654:Taurine; D015240:Phorbol 12,13-Dibutyrate; D002118:Calcium