A subpopulation of rat muscle fibers maintains an assessable excitation-contraction coupling mechanism after long-standing denervation despite lost contractility.
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.
Squecco
Roberta
R
Interuniversitary Institute of Myology, Chieti, Italy.
Carraro
Ugo
U
Kern
Helmut
H
Pond
Amber
A
Adami
Nicoletta
N
Biral
Donatella
D
Vindigni
Vincenzo
V
Boncompagni
Simona
S
Pietrangelo
Tiziana
T
Bosco
Gerardo
G
Fanò
Giorgio
G
Marini
Marina
M
Abruzzo
Provvidenza M
PM
Germinario
Elena
E
Danieli-Betto
Daniela
D
Protasi
Feliciano
F
Francini
Fabio
F
Zampieri
Sandra
S
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
D015220:Calcium Channels; D009124:Muscle Proteins