General continuum theory for multiion channel. II. Application to acetylcholine channel.

Abstract:

:The general theory (Levitt, D. G. 1990. Biophys. J. 59:271-277) is applied to a model channel that resembles the acetylcholine receptor channel (ACH). The model incorporates the known features of the ACH geometry and fixed charge locations. The channel has a wide mouth facing the outer solution, tapering to a narrow region facing the interior of the cell. Rings of fixed negative charge are placed at the two surfaces where the bilayer begins, corresponding to the known charges at the ends of the M2 segment. It is assumed that the forces acting on the ion are electrostatic: ion-channel wall, ion-ion, Born image and applied voltage. Analytical expressions for these forces are derived that take account of the low dielectric lipid region. In addition, there is a local hard sphere repulsive force that prevents ions from piling up on each other in regions of the channel with a high fixed charge density. A classical continuum theory is used to obtain an expression for the diffusion coefficient in the channel. The model can mimic the major qualitative and, in many cases, quantitative experimental features of the ACH channel: current-voltage relation, conductance versus concentration and interaction between monovalent and divalent ions. The model calculations were also compared with the site directed mutagenesis experiments of Imoto, K., C. Busch, B. Sakmann, M. Mishina, T. Konno, J. Nakai, H. Bujo, Y. Mori, K. Fukuda, and S. Numa. (1988. Nature (Lond.). 335:645-648) in which the charge at the ends of the channel was systematically varied.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Levitt DG

doi

10.1016/S0006-3495(91)82221-4

subject

Has Abstract

pub_date

1991-02-01 00:00:00

pages

278-88

issue

2

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(91)82221-4

journal_volume

59

pub_type

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