| First Author | Nayak TK | Year | 2013 |
| Journal | Proc Natl Acad Sci U S A | Volume | 110 |
| Issue | 33 | Pages | 13654-9 |
| PubMed ID | 23898191 | Mgi Jnum | J:200692 |
| Mgi Id | MGI:5509093 | Doi | 10.1073/pnas.1308247110 |
| Citation | Nayak TK, et al. (2013) Asymmetric transmitter binding sites of fetal muscle acetylcholine receptors shape their synaptic response. Proc Natl Acad Sci U S A 110(33):13654-9 |
| abstractText | Neuromuscular acetylcholine receptors (AChRs) have two transmitter binding sites: at alpha-delta and either alpha-gamma (fetal) or alpha-epsilon (adult) subunit interfaces. The gamma-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 alpha-gamma binding site has a higher affinity for ACh and provides more binding energy for gating compared with alpha-epsilon; therefore, the diliganded gating equilibrium constant at -100 mV is comparable for both receptor subtypes. The -2.2 kcal/mol extra binding energy from alpha-gamma compared with alpha-delta and alpha-epsilon 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 alpha-gamma are essential for generating synaptic responses at low pulse [ACh]. |
