TY - JOUR
T1 - Change of chloride ion channel conductance is an early event of slow-to-fast fibre type transition during unloading-induced muscle disuse
AU - Pierno, Sabata
AU - Desaphy, Jean François
AU - Liantonio, Antonella
AU - De Bellis, Michela
AU - Bianco, Gianpatrizio
AU - De Luca, Annamaria
AU - Frigeri, Antonio
AU - Nicchia, G. Paola
AU - Svelto, Maria
AU - Léoty, Claude
AU - George, Alfred L.
AU - Conte Camerino, Diana
N1 - Funding Information:
This work was supported by grants from the Italian Space Agency to D.C.C. (grants ASI ARS-98-71, ASI ARS-99-33, ASI I/R/114/00) and the Italian Telethon Foundation to A.F. (grant 983).
PY - 2002
Y1 - 2002
N2 - 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 CIC-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.
AB - 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 CIC-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.
KW - Chloride channel expression
KW - Fast and slow skeletal muscles
KW - Hindlimb unloading
KW - Mechanical threshold
KW - Muscle plasticity
KW - Myosin heavy chain
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U2 - 10.1093/brain/awf162
DO - 10.1093/brain/awf162
M3 - Article
C2 - 12077001
AN - SCOPUS:0036310087
SN - 0006-8950
VL - 125
SP - 1510
EP - 1521
JO - Brain
JF - Brain
IS - 7
ER -