TTX-sensitive and TTX-insensitive sodium channel mRNA transcripts are independently regulated in adult skeletal muscle after denervation.
The expression of mRNA encoding the TTX-sensitive (SkM1) and TTX-insensitive (SkM2) voltage-dependent sodium channels in adult skeletal muscle is independently regulated. In normal skeletal muscle, only the SkM1 message is expressed and the level varies with muscle fiber type. After surgical denervation, the steady-state SkM1 mRNA level declines transiently, but returns to control levels within 5 days. Expression of SkM2 transcripts is markedly activated, reaching a peak 3 days after axotomy and then declining to a maintained level at approximately 30% of peak. Chemical denervation with botulinum toxin results in higher levels of SkM2 mRNA, which by 7 days posttreatment are 7-fold greater than levels in paired axotomized muscles. SkM2 expression subsequently declines as functional reinnervation appears. Quantal acetylcholine release appears to play a major role in suppression of SkM2 expression in adult innervated or reinnervated muscle, whereas nonquantal factors in toxin-treated, but not axotomized, muscle may sustain high level SkM2 mRNA expression.
Yang
J S
JS
Mahoney Institute of Neurological Sciences, University of Pennsylvania School of Medicine, Philadelphia 19104.
Sladky
J T
JT
Kallen
R G
RG
Barchi
R L
RL
D000818:Animals; D015152:Blotting, Northern; D001905:Botulinum Toxins / Q000494:pharmacology; D003001:Cloning, Molecular; D015870:Gene Expression; D008297:Male; D009121:Muscle Denervation; D009132:Muscles / Q000502:physiology*; D015347:RNA Probes; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains; D015222:Sodium Channels / Q000235:genetics*; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
D015347:RNA Probes; D012333:RNA, Messenger; D015222:Sodium Channels; D013779:Tetrodotoxin; D001905:Botulinum Toxins