Asymmetric transmitter binding sites of fetal muscle acetylcholine receptors shape their synaptic response.
Asymmetric transmitter binding sites of fetal muscle acetylcholine receptors shape their synaptic response.
复制标题
胎儿肌肉乙酰胆碱受体的不对称递质结合位点塑造其突触反应。
DOI：
10.1073/pnas.1308247110
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发表时间：
2013
影响因子：
11.1
通讯作者：
Auerbach,Anthony
中科院分区：
文献类型：
--
作者：
Nayak,TapanK;Auerbach,Anthony
Neuromuscular acetylcholine receptors (AChRs) have two transmitter binding sites: at α−δ and either α−γ (fetal) or α–ε (adult) subunit interfaces. The γ-subunit of fetal AChRs is indispensable for the proper development of neuromuscular synapses. We estimated parameters for acetylcholine (ACh) binding and gating from single channel currents of fetal mouse AChRs expressed in tissue-cultured cells. The unliganded gating equilibrium constant is smaller and less voltage-dependent than in adult AChRs. However, the α−γ binding site has a higher affinity for ACh and provides more binding energy for gating compared with α−ε; therefore, the diliganded gating equilibrium constant at −100 mV is comparable for both receptor subtypes. The −2.2 kcal/mol extra binding energy from α−γ compared with α−δ and α−ε is accompanied by a higher resting affinity for ACh, mainly because of slower transmitter dissociation. End plate current simulations suggest that the higher affinity and increased energy from α−γ are essential for generating synaptic responses at low pulse [ACh].
