Change of chloride ion channel conductance is an early event of slow-to-fast fibre type transition during unloading-induced muscle disuse

Abstract

Disuse of postural slow-twitch muscles, as it occurs in hypogravity, induces a slow-to-fast myofibre type transition. Nothing is known about the effects of weightlessness on the resting membrane chloride conductance (gCl), which controls sarcolemma excitability and influences fibre type transition during development and adult life. Using the current-clamp method, we observed that rat hindlimb unloading (HU) for 1-3 weeks increased gCl in fibres of the slow-twitch soleus (Sol) muscle toward values found in fast muscle. Northern blot analysis suggested that this effect resulted from an increased ClC-1 chloride channel mRNA level. In the meantime, a 4-fold increase in fibres expressing fast isoforms of the myosin heavy chain (MHC) was observed by immunostaining of muscle sections. Also, Sol muscle function evolved toward a fast phenotype during HU, as demonstrated by the positive shift of the threshold potential for contraction. After 3-days HU, Sol muscle immunostaining and RT-PCR experiments revealed no change in MHC protein and mRNA expression, whereas the gCl was already maximally increased, due to a pharmacologically probed, increased activity of ClC-1 channels. Thus the increase in gCl is an early event in Sol muscle experiencing unloading, suggesting that gCl may play a role in muscle adaptation to modified use. Pharmacological modulation of ClC-1 channels may help to prevent disuse-induced muscle impairment.

Fiber Types in Mammalian Skeletal Muscles

“…Studies carried out in rat and mouse muscles show that chloride conductance is higher in fast compared with slow muscle, and this is due to the higher level of expression of ClC1 in fast fibers, but also to the greater inactivation of ClC1 mediated by protein kinase C (PKC) phosphorylation in slow fibers (109,612). Several conditions that induce a fiber type transition are associated with the expected changes in ClC1 expression (611) and with changes in PKC-mediated inactivation (612). C) POTASSIUM CHANNELS.…”

Ion Channel Development, Spontaneous Activity, and Activity-Dependent Development in Nerve and Muscle Cells

“…In mammalian skeletal muscle, innervation upregulates and denervation downregulates I IR expression (205), effects that appear to be secondary to activity-induced increases in [Ca 2ϩ ] i that stabilize IRK1 mRNA (540). Chloride channels also contribute to resting conductance, particularly in skeletal muscle, and their development appears to be dependent on innervation-induced electrical activity (236,293,482).…”

Skeletal muscle atrophy occurs slowly and selectively during prolonged aestivation inCyclorana alboguttata(Günther 1867)

“…Previous studies have shown that immobilisation and unloading can result in a transition from slow to fast myofibres (Roy et al, 1996;Pierno et al, 2002). The transition occurs when the myofibres shift towards a myosin isoform with higher ATPase activity (Diffee et al, 1991).…”