First Author | Takahashi M | Year | 2002 |
Journal | EMBO Rep | Volume | 3 |
Issue | 7 | Pages | 674-81 |
PubMed ID | 12101101 | Mgi Jnum | J:99894 |
Mgi Id | MGI:3584196 | Doi | 10.1093/embo-reports/kvf128 |
Citation | Takahashi M, et al. (2002) Spontaneous muscle action potentials fail to develop without fetal-type acetylcholine receptors. EMBO Rep 3(7):674-81 |
abstractText | 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. |