Cav1.1 controls ATP release to elicit gene expression in adult muscle fibers (1164.12)

Abstract

In adult muscle fibers, Cav1.1 acts as voltage sensor for both excitation‐contraction coupling and the activation of a signaling cascade that regulates gene expression. We have shown that ATP is released through pannexin‐1 channels after electrical stimulation at 20 Hz, having a key role in the induction of transcriptional changes related to fast‐to‐slow muscle fiber phenotype transition. Myotubes lacking the Cav1.1α1 subunit displayed almost no ATP release after electrical stimulation. ATP release and gene transcription was also altered in adult muscle fibers knock‐down for Cav1.1α1.In dystrophic fibers, there was also an increase in basal ATP release, but a default in the stimulation‐dependent increase in ATP release and transcription activation observed in control fibers. This can be interpreted as uncoupling between electrical stimulation and ATP release in dystrophic muscles.All these data suggest that Cav1.1 controls ATP release trough Pannexin‐1 channels, activating it after low stimulation frequencies and blocking ATP release during resting conditions. The loss of this control perturbs the normal transcriptional response to electrical activity of adult muscle fibers and may play a role in the etiology of muscular dystrophy.Grant Funding Source: ACT 1111, FONDECYT 1110467, UINICIA 0212M, CNRS‐CONICYT EDC24748