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This Article Full Text Full Text (PDF) All Versions of this Article: 584/3/983    most recent jphysiol.2007.141358v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Pierno, S. Articles by Conte Camerino, D. Search for Related Content PubMed PubMed Citation Articles by Pierno, S. Articles by Conte Camerino, D. Related Collections Skeletal Muscle and Exercise

¹ Section of Pharmacology, Department of Pharmacobiology, Faculty of Pharmacy, University of Bari, Italy
² Department of Animal Production, Faculty of Veterinary Medicine, University of Bari, Italy
³ Department of General and Environmental Physiology, Faculty of Sciences, University of Bari, Italy

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 PKC, , and 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.

(Received 24 July 2007; accepted after revision 6 September 2007; first published online 13 September 2007)
Corresponding author D. Conte Camerino: Section of Pharmacology, Department of Pharmacobiology, Faculty of Pharmacy, University of Bari, Via Orabona 4 – campus, 70125 Bari, Italy. Email: conte{at}farmbiol.uniba.it