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- Title
Protein kinase C theta (PKCθ) modulates the ClC-1 chloride channel activity and skeletal muscle phenotype: a biophysical and gene expression study in mouse models lacking the PKCθ.
- Authors
Camerino, Giulia; Bouchè, Marina; Bellis, Michela; Cannone, Maria; Liantonio, Antonella; Musaraj, Kejla; Romano, Rossella; Smeriglio, Piera; Madaro, Luca; Giustino, Arcangela; Luca, Annamaria; Desaphy, Jean-François; Camerino, Diana; Pierno, Sabata
- Abstract
In skeletal muscle, the resting chloride conductance (gCl), due to the ClC-1 chloride channel, controls the sarcolemma electrical stability. Indeed, loss-of-function mutations in ClC-1 gene are responsible of myotonia congenita. The ClC-1 channel can be phosphorylated and inactivated by protein kinases C (PKC), but the relative contribution of each PKC isoforms is unknown. Here, we investigated on the role of PKCθ in the regulation of ClC-1 channel expression and activity in fast- and slow-twitch muscles of mouse models lacking PKCθ. Electrophysiological studies showed an increase of gCl in the PKCθ-null mice with respect to wild type. Muscle excitability was reduced accordingly. However, the expression of the ClC-1 channel, evaluated by qRT-PCR, was not modified in PKCθ-null muscles suggesting that PKCθ affects the ClC-1 activity. Pharmacological studies demonstrated that although PKCθ appreciably modulates gCl, other isoforms are still active and concur to this role. The modification of gCl in PKCθ-null muscles has caused adaptation of the expression of phenotype-specific genes, such as calcineurin and myocyte enhancer factor-2, supporting the role of PKCθ also in the settings of muscle phenotype. Importantly, the lack of PKCθ has prevented the aging-related reduction of gCl, suggesting that its modulation may represent a new strategy to contrast the aging process.
- Subjects
PROTEIN kinase C; CHLORIDE channels; SKELETAL muscle; PHENOTYPES; SARCOLEMMA; MYOTONIA congenita; GENE expression
- Publication
Pflügers Archiv: European Journal of Physiology, 2014, Vol 466, Issue 12, p2215
- ISSN
0031-6768
- Publication type
Article
- DOI
10.1007/s00424-014-1495-1