Change of chloride ion channel conductance is an early event of slow-to-fast fibre type transition during unloading-induced muscle disuse.
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.
Pierno
Sabata
S
Sezione di Farmacologia, Dipartimento Farmaco-Biologico, Facoltà di Farmacia, Università degli Studi di Bari, Italy.
Desaphy
Jean-François
JF
Liantonio
Antonella
A
De Bellis
Michela
M
Bianco
Gianpatrizio
G
De Luca
Annamaria
A
Frigeri
Antonio
A
Nicchia
G Paola
GP
Svelto
Maria
M
Léoty
Claude
C
George
Alfred L
AL
Camerino
Diana Conte
DC
D000818:Animals; D015152:Blotting, Northern; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004594:Electrophysiology; D006614:Hindlimb / Q000503:physiopathology; D019417:Hindlimb Suspension; D018472:Hypogravity / Q000009:adverse effects; D007150:Immunohistochemistry; D008297:Male; D009119:Muscle Contraction; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism* / Q000473:pathology; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism* / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology / Q000503:physiopathology*; D020966:Muscular Disorders, Atrophic / Q000473:pathology / Q000503:physiopathology*; D018995:Myosin Heavy Chains / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012508:Sarcolemma / Q000378:metabolism
D018118:Chloride Channels; D002712:Chlorides; D020033:Protein Isoforms; D012333:RNA, Messenger; D018995:Myosin Heavy Chains