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 journalArticle

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

Fingerprint

Excitation Contraction Coupling
Denervation
Muscles
Electric Stimulation
Gene Expression
L-Type Calcium Channels
Ryanodine Receptor Calcium Release Channel
Muscular Atrophy
Contracture
Caffeine
Atrophy
Leg
Rehabilitation
Genes

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

Cite this

A subpopulation of rat muscle fibers maintains an assessable excitation-contraction coupling mechanism after long-standing denervation despite lost contractility. / Squecco, Roberta; Carraro, Ugo; Kern, Helmut; Pond, Amber; Adami, Nicoletta; Biral, Donatella; Vindigni, Vincenzo; Boncompagni, Simona; Pietrangelo, Tiziana; Bosco, Gerardo; Fanò, Giorgio; Marini, Marina; Abruzzo, Provvidenza M.; Germinario, Elena; Danieli-Betto, Daniela; Protasi, Feliciano; Francini, Fabio; Zampieri, Sandra.

In: Journal of Neuropathology and Experimental Neurology, Vol. 68, No. 12, 12.2009, p. 1256-1268.

Research output: Contribution to journalArticle

Squecco, R, Carraro, U, Kern, H, Pond, A, Adami, N, Biral, D, Vindigni, V, Boncompagni, S, Pietrangelo, T, Bosco, G, Fanò, G, Marini, M, Abruzzo, PM, Germinario, E, Danieli-Betto, D, Protasi, F, Francini, F & Zampieri, S 2009, 'A subpopulation of rat muscle fibers maintains an assessable excitation-contraction coupling mechanism after long-standing denervation despite lost contractility', Journal of Neuropathology and Experimental Neurology, vol. 68, no. 12, pp. 1256-1268. https://doi.org/10.1097/NEN.0b013e3181c18416
Squecco, Roberta ; Carraro, Ugo ; Kern, Helmut ; Pond, Amber ; Adami, Nicoletta ; Biral, Donatella ; Vindigni, Vincenzo ; Boncompagni, Simona ; Pietrangelo, Tiziana ; Bosco, Gerardo ; Fanò, Giorgio ; Marini, Marina ; Abruzzo, Provvidenza M. ; Germinario, Elena ; Danieli-Betto, Daniela ; Protasi, Feliciano ; Francini, Fabio ; Zampieri, Sandra. / A subpopulation of rat muscle fibers maintains an assessable excitation-contraction coupling mechanism after long-standing denervation despite lost contractility. In: Journal of Neuropathology and Experimental Neurology. 2009 ; Vol. 68, No. 12. pp. 1256-1268.
@article{5b29b05dd96644b69ae237f1c3d87544,
title = "A subpopulation of rat muscle fibers maintains an assessable excitation-contraction coupling mechanism after long-standing denervation despite lost contractility",
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.",
keywords = "DHPR, Excitation-contraction coupling, Gene expression, L-Type Ca2+ current, Long-term denervation, RYR-1 Ca2+ channels, Sarcotubular system",
author = "Roberta Squecco and Ugo Carraro and Helmut Kern and Amber Pond and Nicoletta Adami and Donatella Biral and Vincenzo Vindigni and Simona Boncompagni and Tiziana Pietrangelo and Gerardo Bosco and Giorgio Fan{\`o} and Marina Marini and Abruzzo, {Provvidenza M.} and Elena Germinario and Daniela Danieli-Betto and Feliciano Protasi and Fabio Francini and Sandra Zampieri",
year = "2009",
month = "12",
doi = "10.1097/NEN.0b013e3181c18416",
language = "English",
volume = "68",
pages = "1256--1268",
journal = "American Journal of Psychotherapy",
issn = "0002-9564",
publisher = "Lippincott Williams and Wilkins",
number = "12",

}

TY - JOUR

T1 - A subpopulation of rat muscle fibers maintains an assessable excitation-contraction coupling mechanism after long-standing denervation despite lost contractility

AU - Squecco, Roberta

AU - Carraro, Ugo

AU - Kern, Helmut

AU - Pond, Amber

AU - Adami, Nicoletta

AU - Biral, Donatella

AU - Vindigni, Vincenzo

AU - Boncompagni, Simona

AU - Pietrangelo, Tiziana

AU - Bosco, Gerardo

AU - Fanò, Giorgio

AU - Marini, Marina

AU - Abruzzo, Provvidenza M.

AU - Germinario, Elena

AU - Danieli-Betto, Daniela

AU - Protasi, Feliciano

AU - Francini, Fabio

AU - Zampieri, Sandra

PY - 2009/12

Y1 - 2009/12

N2 - 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.

AB - 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.

KW - DHPR

KW - Excitation-contraction coupling

KW - Gene expression

KW - L-Type Ca2+ current

KW - Long-term denervation

KW - RYR-1 Ca2+ channels

KW - Sarcotubular system

UR - http://www.scopus.com/inward/record.url?scp=73349099040&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=73349099040&partnerID=8YFLogxK

U2 - 10.1097/NEN.0b013e3181c18416

DO - 10.1097/NEN.0b013e3181c18416

M3 - Article

C2 - 19915489

AN - SCOPUS:73349099040

VL - 68

SP - 1256

EP - 1268

JO - American Journal of Psychotherapy

JF - American Journal of Psychotherapy

SN - 0002-9564

IS - 12

ER -