Spontaneous muscle action potentials fail to develop without fetal-type acetylcholine receptors |
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Authors: | Takahashi Masazumi Kubo Tai Mizoguchi Akira Carlson C George Endo Katsuaki Ohnishi Katsunori |
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Affiliation: | International Institute for Advanced Studies, Numa Project, Nishinokyo-Kuwaharacho, Shimadzu, Nakagyo, Kyoto, Japan. masazumi@cng.fr |
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Abstract: | In mammals, two combinations of muscle nicotinic acetylcholine receptors (AChRs) are used: α2βγδ (γ-AChR) or α2βδ (-AChR). After birth, γ-AChRs are replaced by -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 (mEPPs). -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. |
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