Cav1.1 controls frequency-dependent events regulating adult skeletal muscle plasticity

Gonzalo Jorquera, Francisco Altamirano, Ariel Contreras-Ferrat, Gonzalo Almarza, Sonja Buvinic, Vincent Jacquemond, Enrique Jaimovich, Mariana Casas

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

An important pending question in neuromuscular biology is how skeletal muscle cells decipher the stimulation pattern coming from motoneurons to define their phenotype as slow or fast twitch muscle fibers. We have previously shown that voltage-gated L-type calcium channel (Cav1.1) acts as a voltage sensor for activation of inositol (1,4,5)-trisphosphate [Ins(1,4,5)P3]-dependent Ca2+ signals that regulates gene expression. ATP released by muscle cells after electrical stimulation through pannexin-1 channels plays a key role in this process. We show now that stimulation frequency determines both ATP release and Ins(1,4,5)P3 production in adult skeletal muscle and that Cav1.1 and pannexin-1 colocalize in the transverse tubules. Both ATP release and increased Ins(1,4,5)P3 was seen in flexor digitorum brevis fibers stimulated with 270 pulses at 20 Hz, but not at 90 Hz. 20 Hz stimulation induced transcriptional changes related to fast-to-slow muscle fiber phenotype transition that required ATP release. Addition of 30 mM ATP to fibers induced the same transcriptional changes observed after 20 Hz stimulation. Myotubes lacking the Cav1.1-a1 subunit released almost no ATP after electrical stimulation, showing that Cav1.1 has a central role in this process. In adult muscle fibers, ATP release and the transcriptional changes produced by 20 Hz stimulation were blocked by both the Cav1.1 antagonist nifedipine (25 mM) and by the Cav1.1 agonist (-)SBayK 8644 (10 mM). We propose a new role for Cav1.1, independent of its calcium channel activity, in the activation of signaling pathways allowing muscle fibers to decipher the frequency of electrical stimulation and to activate specific transcriptional programs that define their phenotype.

Original languageEnglish (US)
Pages (from-to)1189-1198
Number of pages10
JournalJournal of Cell Science
Volume126
Issue number5
DOIs
StatePublished - Mar 1 2013

Keywords

  • DHPR
  • Excitation-transcription coupling
  • Extracellular ATP
  • Frequency decoding
  • Gene expression
  • Muscle plasticity

ASJC Scopus subject areas

  • Cell Biology

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