Calcium influx blocks the skeletal muscle acetylcholine receptor alpha-subunit gene in vivo

C F Huang1, J Schmidt

  • 1Department of Biochemistry and Cell Biology, State University of New York at Stony Brook 11794.

FEBS Letters
|February 7, 1994
PubMed

Insights

Calcium influx into denervated muscle cells regulates acetylcholine receptor gene activity. Calcium-active drugs mimicked or blocked electrostimulation effects, highlighting calcium's role in gene inactivation.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Muscle Physiology

Background:

  • Denervation of skeletal muscle leads to changes in acetylcholine receptor (AChR) gene expression.
  • Electrostimulation can reverse some denervation-induced changes in gene transcription.
  • The role of intracellular calcium signaling in regulating AChR gene activity remains incompletely understood.

Purpose of the Study:

  • To investigate the role of extracellular calcium influx in the transcriptional regulation of the acetylcholine receptor alpha-subunit gene in denervated chick skeletal muscle.
  • To determine if calcium-active drugs can mimic or block the effects of electrostimulation on AChR gene transcription.

Main Methods:

  • Utilized a ribonuclease protection assay, a variation of the conventional run-off assay, to measure transcriptional activity.
  • Applied L-channel agonist (-)Bay-K6844, calcium ionophore A23187, intracellular chelator BAPTA, and calcium channel blockers D600 and nifedipine to denervated chick skeletal muscle.
  • Compared the effects of these drugs to electrostimulation.

Main Results:

  • The L-channel agonist (-)Bay-K6844 and calcium ionophore A23187 replicated the effects of electrostimulation on AChR gene transcription.
  • Intracellular chelator BAPTA and calcium channel blockers D600 and nifedipine inhibited the effects of electrostimulation.
  • These findings indicate that calcium influx is crucial for the observed changes in gene activity.

Conclusions:

  • Extracellular calcium influx is a critical component of the signaling pathway that leads to the inactivation of the acetylcholine receptor gene following membrane depolarization.
  • Modulating calcium levels can influence the transcriptional activity of the AChR alpha-subunit gene in denervated muscle.
  • These findings provide insights into the molecular mechanisms underlying muscle gene regulation and potential therapeutic targets.

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