Differential influence of electrical blocking agents on embryonic acetylcholine receptor mRNA levels in long-term cultures of aneural mammalian myotubes.
The influence of spontaneous muscle activity on acetylcholine receptor (AChR) expression was examined by exposing long-term cultures of mammalian myotubes to two pharmacological agents that have similar effects on the rate of spontaneous contractile activity but pharmacologically distinct actions on voltage gated Na+ channels. Previous studies by other investigators have shown that tetrodotoxin upregulates and that veratridine downregulates surface AChR expression in short-term mammalian muscle cultures. In order to determine whether these drugs have disparate actions on AChR mRNA levels, myotubes were exposed to either tetrodotoxin or veratridine for a period of 10 days, and measurements of the relative levels of embryonic AChR subunit mRNAs (alpha, beta, gamma, delta) were obtained during and following the period of drug exposure. Veratridine produced a substantial decrease (between 33% and 50% reduction), while tetrodotoxin produced a relatively small increase (between 17% and 23%), in each of the AChR subunit mRNAs after 6 days of drug exposure. At 23 days in culture, spontaneously active myotubes exhibited a decrease in the relative levels of each of the AChR subunit mRNAs. Myotubes previously exposed to either veratridine or tetrodotoxin exhibited elevated levels of beta, gamma, and delta AChR subunit mRNAs 6 days after cessation of drug treatment, thus suggesting that a period of muscle inactivity can induce sustained influences on some AChR mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Carlson
C G
CG
Department of Physiology, University of North Dakota, School of Medicine, Grand Forks 58202.
Adkins
S D
SD
Blake
M J
MJ
Hasan
A K
AK
Loyland
S
S
D000818:Animals; D001345:Autoradiography; D015152:Blotting, Northern; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004594:Electrophysiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008870:Microtubules / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000196:embryology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology*; D014701:Veratridine / Q000494:pharmacology*
D012333:RNA, Messenger; D011950:Receptors, Cholinergic; D013779:Tetrodotoxin; D014701:Veratridine; D012964:Sodium; D002118:Calcium