Premium
Disuse of rat muscle in vivo reduces protein kinase C activity controlling the sarcolemma chloride conductance
Author(s) -
Pierno Sabata,
Desaphy JeanFrançois,
Liantonio Antonella,
De Luca Annamaria,
Zarrilli Antonia,
Mastrofrancesco Lisa,
Procino Giuseppe,
Valenti Giovanna,
Conte Camerino Diana
Publication year - 2007
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2007.141358
Subject(s) - sarcolemma , protein kinase c , chemistry , phosphatase , threonine , endocrinology , medicine , chloride channel , phosphorylation , fast twitch muscle , serine , extensor digitorum longus muscle , in vivo , biophysics , myocyte , skeletal muscle , biochemistry , biology , microbiology and biotechnology
Muscle disuse produced by hindlimb unloading (HU) induces severe atrophy and slow‐to‐fast fibre type transition of the slow‐twitch soleus muscle (Sol). After 2 weeks HU, the resting ClC‐1 chloride conductance ( g Cl ) of sarcolemma, which controls muscle excitability, increases in Sol toward a value typical of the fast‐twitch EDL muscle. After 3 days of HU, the g Cl increases as well before initiation of fibre type transition. Since ClC‐1 channels are acutely silenced by PKC‐dependent phosphorylation, we studied the modulation of g Cl by PKC and serine–threonine phosphatase in Sol during HU, using a number of pharmacological tools. We show that a fraction of ClC‐1 channels of control Sol are maintained in an inactive state by PKC basal activity, which contributes to the lower g Cl in control Sol compared to EDL. After 14 days of HU, PKC/phosphatase manipulation produces effects on Sol g Cl that corroborate the partial slow‐to‐fast transition. After 3 days of HU, the early increase of g Cl in Sol is entirely attributable to a reduction of PKC activity and/or activation of phosphatase, maintaining ClC‐1 channels in a fully active state. Accordingly, we found that HU reduces expression of PKCα, ɛ, and θ isoenzymes in Sol and EDL muscles and reduces total PKC activity. Moreover, we show that the rheobase current is increased in Sol muscle fibres as soon as after 3 days of HU, most probably in relation to the increased g Cl . In conclusion, Sol muscle disuse is characterized by a rapid reduction of PKC activity, which reduces muscle excitability and is likely to contribute to disuse‐induced muscle impairment.