title: Control of cation permeation through the nicotinic receptor channel.
abstract: We used molecular dynamics (MD) simulations to explore the transport of single cations through the channel of the muscle nicotinic acetylcholine receptor (nAChR). Four MD simulations of 16 ns were performed at physiological and hyperpolarized membrane potentials, with and without restraints of the structure, but all without bound agonist. With the structure unrestrained and a potential of -100 mV, one cation traversed the channel during a transient period of channel hydration; at -200 mV, the channel was continuously hydrated and two cations traversed the channel. With the structure restrained, however, cations did not traverse the channel at either membrane potential, even though the channel was continuously hydrated. The overall results show that cation selective transport through the nAChR channel is governed by electrostatic interactions to achieve charge selectivity, but ion translocation relies on channel hydration, facilitated by a trans-membrane field, coupled with dynamic fluctuations of the channel structure.
authors.affiliation: Receptor Biology Laboratory, Department of Physiology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. hwang@mayo.edu
authors.forename: Hai-Long
authors.initials: HL
authors.lastname: Wang
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Cheng
authors.forename: Palmer
authors.initials: P
authors.lastname: Taylor
authors.forename: J Andrew
authors.initials: JA
authors.lastname: McCammon
authors.forename: Steven M
authors.initials: SM
authors.lastname: Sine
mesh_terms: D002412:Cations; D003198:Computer Simulation; D004574:Electromagnetic Fields; D015640:Ion Channel Gating; D008051:Lipid Bilayers / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D009038:Motion; D010539:Permeability; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000648:ultrastructure*
chemical_list: D002412:Cations; D008051:Lipid Bilayers; D011978:Receptors, Nicotinic