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 and electrophysiological 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 lost nerve 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 response to rehabilitation strategies developed based on empirical clinical observations.
authors.affiliation: Interuniversitary Institute of Myology, Chieti, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Squecco
authors.forename: Ugo
authors.initials: U
authors.lastname: Carraro
authors.forename: Helmut
authors.initials: H
authors.lastname: Kern
authors.forename: Amber
authors.initials: A
authors.lastname: Pond
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Adami
authors.forename: Donatella
authors.initials: D
authors.lastname: Biral
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Vindigni
authors.forename: Simona
authors.initials: S
authors.lastname: Boncompagni
authors.forename: Tiziana
authors.initials: T
authors.lastname: Pietrangelo
authors.forename: Gerardo
authors.initials: G
authors.lastname: Bosco
authors.forename: Giorgio
authors.initials: G
authors.lastname: Fanò
authors.forename: Marina
authors.initials: M
authors.lastname: Marini
authors.forename: Provvidenza M
authors.initials: PM
authors.lastname: Abruzzo
authors.forename: Elena
authors.initials: E
authors.lastname: Germinario
authors.forename: Daniela
authors.initials: D
authors.lastname: Danieli-Betto
authors.forename: Feliciano
authors.initials: F
authors.lastname: Protasi
authors.forename: Fabio
authors.initials: F
authors.lastname: Francini
authors.forename: Sandra
authors.initials: S
authors.lastname: Zampieri
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D015870:Gene Expression; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D046529:Microscopy, Electron, Transmission; D009119:Muscle Contraction / Q000502:physiology*; D009121:Muscle Denervation / Q000009:adverse effects*; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics; D018482:Muscle, Skeletal / Q000502:physiology*; D009133:Muscular Atrophy / Q000503:physiopathology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015220:Calcium Channels; D009124:Muscle Proteins