ELECTROSTATICS AND THE ION SELECTIVITY OF LIGAND-GATED CHANNELS

Citation
C. Adcock et al., ELECTROSTATICS AND THE ION SELECTIVITY OF LIGAND-GATED CHANNELS, Biophysical journal, 75(3), 1998, pp. 1211-1222
Citations number
74
Categorie Soggetti
Biophysics
Journal title
ISSN journal
00063495
Volume
75
Issue
3
Year of publication
1998
Pages
1211 - 1222
Database
ISI
SICI code
0006-3495(1998)75:3<1211:EATISO>2.0.ZU;2-0
Abstract
The nicotinic acetylcholine receptor (nAChR) is a cation-selective ion channel that opens in response to acetylcholine binding. The related glycine receptor (GlyR) is anion selective. The pore-lining domain of each protein may be modeled as a bundle of five parallel M2 helices. M odels of the pore-lining domains of homopentameric nAChR and GlyR have been used in continuum electrostatics calculations to probe the origi ns of ion selectivity. Calculated pK(A), values suggest that ''rings'' of acidic or basic side chains at the mouths of the nAChR or GlyR M2 helix bundles, respectively, may not be fully ionized. In particular, for the nAChR the ring of glutamate side chains at the extracellular m outh of the pore is predicted to be largely protonated at neutral pH, whereas those glutamate side chains in the intracellular and intermedi ate rings (at the opposite mouth of the pore) are predicted to be full y ionized. Inclusion of the other domains of each protein represented as an irregular cylindrical tube in which the M2 bundles are embedded suggests that both the M2 helices and the extramembrane domains play s ignificant roles in determining ion selectivity.