A subpopulation of rat muscle fibers maintains an assessable excitation-contraction coupling mechanism after long-standing denervation despite lost contractility

Roberta Squecco, Ugo Carraro, Helmut Kern, Amber Pond, Nicoletta Adami, Donatella Biral, Vincenzo Vindigni, Simona Boncompagni, Tiziana Pietrangelo, Gerardo Bosco, Giorgio Fanò, Marina Marini, Provvidenza M. Abruzzo, Elena Germinario, Daniela Danieli-Betto, Feliciano Protasi, Fabio Francini, Sandra Zampieri

Research output: Contribution to journalArticlepeer-review

Abstract

To define the time course and potential effects of electrical stimulation on permanently denervated muscle, we evaluated excitation-contraction coupling (ECC) of rat leg muscles during progression to long-term denervation by ultrastructural analysis, specific binding to dihydropyridine receptors, ryanodine receptor 1 (RYR-1), Ca channels and extrusion Ca pumps, gene transcription and translation of Ca-handling proteins, and in vitro mechanical properties andelectrophysiological analyses of sarcolemmal passive properties and L-type Ca current (ICa) parameters. We found that in response to long-term denervation: 1) isolated muscle that is unable to twitch in vitro by electrical stimulation has very small myofibers but may show a slow caffeine contracture; 2) only roughly half of the muscle fibers with "voltage-dependent Ca channel activity" are able to contract; 3) the ECC mechanisms are still present and, in part, functional; 4)ECC-related gene expression is upregulated; and 5) at any time point, there are muscle fibers that are more resistant than others to denervation atrophy and disorganization of the ECC apparatus. These results support the hypothesis that prolonged "resting" [Ca] may drive progression of muscle atrophy to degeneration and that electrical stimulation-induced [Ca] modulation may mimic the lostnerve influence, playing a key role in modifying the gene expression of denervated muscle. Hence, these data provide a potential molecular explanation for the muscle recovery that occurs in responseto rehabilitation strategies developed based on empirical clinical observations.

Original languageEnglish
Pages (from-to)1256-1268
Number of pages13
JournalJournal of Neuropathology and Experimental Neurology
Volume68
Issue number12
DOIs
Publication statusPublished - Dec 2009

Keywords

  • DHPR
  • Excitation-contraction coupling
  • Gene expression
  • L-Type Ca2+ current
  • Long-term denervation
  • RYR-1 Ca2+ channels
  • Sarcotubular system

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Neurology
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'A subpopulation of rat muscle fibers maintains an assessable excitation-contraction coupling mechanism after long-standing denervation despite lost contractility'. Together they form a unique fingerprint.

Cite this