Hydrophobic Selectivity And Electrostatic Gating In Narrow Ion Channels

Abstract

Previous studies have shown that some ion channels, such as the nicotinic acetylcholine receptors (nAChR), have a hydrophobic region lining the pore in the transmembrane domain (TM-domain) that is responsible for gating the channel, and a charged ring at the extracellular entrance of the TM-domain which is important for ion selectivity. Our recent studies show that the hydrophobic effect can also contribute to the ion selectivity, and the electrostatic effect can also play a role in the gating behavior.1) Hydrophobic selectivity: Singe walled carbon nanotubes (SWNTs) are selected as the model of the hydrophobic pores and potential of mean force calculations are performed for Na+, K+ and Cl- respectively. The results show that for the (8,8) and (9,9) SWNTs which ions can pass through under biological driving forces, the free energy difference between types of ions can exceed 2 kcal/mol. This difference arises mainly from the differing dehydration energies and this hydrophobic selectivity may complement electrostatic origins of selectivity.2) Electrostatic gating: Preliminary electrostatic calculation results on the TM-domain of the nAChR in the closed state show that a ring of charged residues can tightly bind an ion preventing conduction. A small conformational change of the protein that increases pore radius by only 0.5 A can reduce the binding by ∼6 kcal/mol and allow permeation.