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

• Published in: EMBO reports Vol. 3; no. 7; pp. 674 - 681
• Main Authors: Takahashi, Masazumi, Kubo, Tai, Mizoguchi, Akira, Carlson, C George, Endo, Katsuaki, Ohnishi, Katsunori
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01-07-2002; Blackwell Publishing Ltd; Oxford University Press
• Subjects: Action Potentials - physiology; Animals; Animals, Newborn; Bungarotoxins - metabolism; Excitatory Postsynaptic Potentials; Female; Fetus - physiology; Fluorescent Dyes - metabolism; Gene Targeting; Immunohistochemistry; Mice; Mice, Inbred C57BL; Muscle Fibers, Skeletal - cytology; Muscle Fibers, Skeletal - metabolism; Muscle, Skeletal - cytology; Muscle, Skeletal - physiology; Neuromuscular Junction - metabolism; Neuromuscular Junction - ultrastructure; Phrenic Nerve - cytology; Phrenic Nerve - metabolism; Protein Subunits; Receptors, Cholinergic - genetics; Receptors, Cholinergic - metabolism; Scientific Reports
• ISSN: 1469-221X; 1469-3178
• DOI: 10.1093/embo-reports/kvf128

In mammals, two combinations of muscle nicotinic acetylcholine receptors (AChRs) are used: α2βγδ (γ‐AChR) or α2βϵδ (ϵ‐AChR). After birth, γ‐AChRs are replaced by ϵ‐AChRs (γ/ϵ‐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 (mEPPs). ϵ‐AChRs are suitable for strong adult muscle activities. Since the effect of the γ/ϵ‐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 ϵ‐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.