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- Title
Spontaneous muscle action potentials fail to develop without fetal-type acetylcholine receptors.
- Authors
Takahashi, Masazumi; Kubo, Tai; Mizoguchi, Akira; Carlson, C. George; Endo, Katsuaki; Ohnishi, Katsunori
- Abstract
In mammals, two combinations of muscle nicotinic acetylcholine receptors (AChRs) are used: α2βγδ (γ-AChR) or α2β∊δ (∊-AChR). After birth, γ-AChRs are replaced by &apsi;-AChRs (`γ/∊-switch). The two receptors have different conductances and open times. During perinatal period, the long open time γ-AChRs generate random myofiber action potentials from uniquantal miniature end-plate potentials (mEPP5). ϵ-AChRs are suitable for strong adult muscle activities. Since the effect of the γ/∊-switch on neuromuscular development was unclear, despite the many differences in channel characteristics, we carried out this study to generate γ-subunit-deficient mice. Homozygotes born alive survived for 2 days in a stable condition, and were able to move their forelimbs. Endplate AChRs included ∊-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 γ-AChRs in mediating synaptically-induced action potential activity critical for neuromuscular development.
- Subjects
NICOTINIC receptors; CHOLINERGIC receptors; FORELIMB; MYONEURAL junction; NEUROTRANSMITTER receptors; EXTREMITIES (Anatomy)
- Publication
EMBO Reports, 2002, Vol 3, Issue 7, p674
- ISSN
1469-221X
- Publication type
Report
- DOI
10.1093/embo-reports/kvf128