Skeletal muscle disuse induces fibre type-dependent enhancement of Na+ channel expression

Slow-twitch and fast-twitch muscle fibres have specific contractile propert ies to respond to specific needs, Since sodium current density is higher in fast-twitch than in slow-twitch fibres, sodium channels contribute to the phenotypic feature of myofibres, Phenotype determination is not irreversibl e: after periods of rat hindlimb unloading (HU), a model of hypogravity, a slow-to-fast transition occurs together with atrophy in the antigravity slo w-twitch soleus muscle, Using cell-attached patch-clamp and northern blot a nalyses, we looked at sodium channel expression in soleus muscles after 1-3 weeks of HU in rats. We found that sodium channels in fast-twitch flexor d igitorum brevis muscle fibres, soleus muscle fibres and 1- to 3-week HU sol eus muscle fibres showed no difference in unitary conductance, open probabi lity and voltage-dependencies of activation, fast inactivation and slow ina ctivation, However, muscle disuse increased sodium current density in soleu s muscle fibres 2-fold, 2.5-fold and 3-fold after 1, 2 and 3 weeks of HU, r espectively. The concentration of mRNA for the skeletal muscle sodium chann el or subunit increased 2-fold after 1 week of HU but returned to the contr ol level after 3 weeks of HU, In contrast, the concentration of mRNA for th e ubiquitous sodium channel beta1 subunit was unchanged after 1 week and ha d increased by 30% after 3 weeks of HU, The tetrodotoxin sensitivity of sod ium currents in 3-week HU soleus muscles and the lack of mRNA signal for th e juvenile skeletal muscle sodium channel a subunit excluded denervation in our experiments, The observed increase in sodium current density may reduc e the resistance to fatigue of antigravity muscle fibres, an effect that ma y contribute to muscle impairment in humans after space flight or after lon g immobilization.