MODIFICATION BY AGING OF THE TETRODOTOXIN-SENSITIVE SODIUM-CHANNELS IN RAT SKELETAL-MUSCLE FIBERS

Ageing leads to an impairment of muscle performance that may result fr om alteration of sarcolemma excitability. Therefore, we compare sodium channels of native fast-twitch skeletal muscle fibres of 21-26-month- old aged rats and 4-6-month-old young-adult rats, using the patch-clam p method. Extrajunctional sarcolemma of aged-rat fibres presented a hi gher sodium current density than that of young-rat fibres, which resul ted from the presence of a higher number of available channels per mem brane area. Open probability and availability voltage-dependence of so dium channels were similar in aged- and young-rat fibres, but permeati on property was altered during ageing: aged-rat muscles showed a bimod al distribution of fibres with two values of sodium-channel conductanc e measured between -40 and 0 mV; a young phenotype with a conductance close to 18 pS overlapping that found in young-rat fibres and an aged phenotype with a lower approximately half conductance. Current-voltage curves extended to -60 and +20 mV showed that the aged-phenotype cond uctance level resulted from an outward rectification occurring in thes e aged-rat fibres. Furthermore, in these aged-rat fibres belonging to the aged phenotype, ensemble average sodium currents showed slower act ivation and Inactivation kinetics. Sodium currents of the two phenotyp es were blocked by 100 nM tetrodotoxin, therefore excluding possible d enervation effect. These age-related modifications in sodium current m ay contribute to the alteration of muscle excitability and function ob served during the ageing process. (C) 1998 Elsevier Science B.V. All r ights reserved.