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.
Takahashi
Masazumi
M
International Institute for Advanced Studies, Numa Project, Nishinokyo-Kuwaharacho, Shimadzu, Nakagyo, Kyoto, Japan. masazumi@cng.fr
Kubo
Tai
T
Mizoguchi
Akira
A
Carlson
C George
CG
Endo
Katsuaki
K
Ohnishi
Katsunori
K
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D002038:Bungarotoxins / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials; D005260:Female; D005333:Fetus / Q000502:physiology*; D005456:Fluorescent Dyes / Q000378:metabolism; D018390:Gene Targeting; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D009469:Neuromuscular Junction / Q000378:metabolism / Q000648:ultrastructure; D010791:Phrenic Nerve / Q000166:cytology / Q000378:metabolism; D021122:Protein Subunits; D011950:Receptors, Cholinergic / Q000235:genetics / Q000378:metabolism*
D002038:Bungarotoxins; D005456:Fluorescent Dyes; D021122:Protein Subunits; D011950:Receptors, Cholinergic