Nav1.4 and Nav1.5 are modulated differently during muscle immobilization and contractile phenotype conversion

Abstract

Muscle immobilization leads to modification in its fast/slow contractile phenotype. Since the properties of voltage-gated sodium channels (Na(v)) are different between "fast" and "slow" muscles, we studied the effects of immobilization on the contractile properties and the Na(v) of rat peroneus longus (PL). The distal tendon of PL was cut and fixed to the adjacent bone at neutral muscle length. After 4 or 8 wk of immobilization, the contractile and the Na(v) properties were studied and compared with muscles from control animals (Student's t-test). After 4 wk of immobilization, PL showed a faster phenotype with a rightward shift of the force-frequency curve and a decrease in both the Burke's index of fatigability and the tetanus-to-twitch ratio. These parameters showed opposite changes between 4 and 8 wk of immobilization. The maximal sodium current in 4-wk immobilized fibers was higher compared with that of control fibers (11.5 ± 1.2 vs. 7.8 ± 0.8 nA, P = 0.008), with partial recovery to the control values in 8-wk immobilized fibers (8.6 ± 0.7 nA, P = 0.48). In the presence of tetrodotoxin, the maximal residual sodium current decreased continuously throughout immobilization. Using the Western blot analysis, Na(v)1.4 expression showed a transient increase in 4-wk muscle, whereas Na(v)1.5 expression decreased during immobilization. Our results indicate that a muscle immobilized at optimal functional length with the preservation of neural inputs exhibits a transient fast phenotype conversion. Na(v)1.4 expression and current are related to the contractile phenotype variation.