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Spontaneous muscle action potentials fail to develop without fetal-type acetylcholine receptors.

In mammals, two combinations of muscle nicotinic acetylcholine receptors (AChRs) are used: alpha2betagammadelta (gamma-AChR) or alpha2betaepsilondelta (epsilon-AChR). After birth, gamma-AChRs are replaced by epsilon-AChRs (gamma/epsilon-switch). The two receptors have different conductances and open times. During perinatal period, the long open time gamma-AChRs generate random myofiber action potentials from uniquantal miniature end-plate potentials (mEPPs). epsilon-AChRs are suitable for strong adult muscle activities. Since the effect of the gamma/epsilon-switch on neuromuscular development was unclear, despite the many differences in channel characteristics, we carried out this study to generate gamma-subunit-deficient mice. Homozygotes born alive survived for 2 days in a stable condition, and were able to move their forelimbs. Endplate AChRs included epsilon-subunits, and muscle fibers had multiple neuromuscular junctions. Both pre- and postsynapses were abnormal and spontaneous action potentials generated from mEPPs were totally absent. Results suggest a requirement for gamma-AChRs in mediating synaptically-induced action potential activity critical for neuromuscular development.

Pubmed ID: 12101101


  • Takahashi M
  • Kubo T
  • Mizoguchi A
  • Carlson CG
  • Endo K
  • Ohnishi K


EMBO reports

Publication Data

July 8, 2002

Associated Grants


Mesh Terms

  • Action Potentials
  • Animals
  • Animals, Newborn
  • Bungarotoxins
  • Excitatory Postsynaptic Potentials
  • Female
  • Fetus
  • Fluorescent Dyes
  • Gene Targeting
  • Immunohistochemistry
  • Mice
  • Mice, Inbred C57BL
  • Muscle Fibers, Skeletal
  • Muscle, Skeletal
  • Neuromuscular Junction
  • Phrenic Nerve
  • Protein Subunits
  • Receptors, Cholinergic