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

Slow-twitch and fast-twitch muscle fibres have specific contractile properties 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 irreversible: after periods of rat hindlimb unloading (HU), a model of hypogravity, a slow-to-fast transition occurs together with atrophy in the antigravity slow-twitch soleus muscle. Using cell-attached patch-clamp and northern blot analyses, 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 digitorum brevis muscle fibres, soleus muscle fibres and 1- to 3-week HU soleus muscle fibres showed no difference in unitary conductance, open probability and voltage-dependencies of activation, fast inactivation and slow inactivation. However, muscle disuse increased sodium current density in soleus muscle fibres 2-fold, 2.5-fold and 3-fold after 1, 2 and 3 weeks of HU, respectively. The concentration of mRNA for the skeletal muscle sodium channel alpha subunit increased 2-fold after 1 week of HU but returned to the control level after 3 weeks of HU. In contrast, the concentration of mRNA for the ubiquitous sodium channel beta(1) subunit was unchanged after 1 week and had increased by 30% after 3 weeks of HU. The tetrodotoxin sensitivity of sodium currents in 3-week HU soleus muscles and the lack of mRNA signal for the juvenile skeletal muscle sodium channel alpha subunit excluded denervation in our experiments. The observed increase in sodium current density may reduce the resistance to fatigue of antigravity muscle fibres, an effect that may contribute to muscle impairment in humans after space flight or after long immobilization.