Channelpedia

PubMed 24643479


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: ClvC1 , ClvC4 , Slo1



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: Giulia Maria Camerino, Marina Bouché, Michela De Bellis, Maria Cannone, Antonella Liantonio, Kejla Musaraj, Rossella Romano, Piera Smeriglio, Luca Madaro, Arcangela Giustino, Annamaria De Luca, Jean-François Desaphy, Diana Conte Camerino, Sabata Pierno

Journal, date & volume: Pflugers Arch., 2014 Dec , 466, 2215-28

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24643479


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.