Referenced in: none

Automatically associated channels: Kv2.1 , Kv3.1

Title: Mutational analysis of ion conduction and drug binding sites in the inner mouth of voltage-gated K+ channels.

Authors: C C Shieh, G E Kirsch

Journal, date & volume: Biophys. J., 1994 Dec , 67, 2316-25

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/7696472

Abstract
Pore properties that distinguish two cloned, voltage-gated K+ channels, Kv2.1 and Kv3.1, include single-channel conductance, block by external and internal tetraethylammonium, and block by 4-aminopyridine. To define the inner mouth of voltage-gated K+ channels, segmental exchanges and point mutations of nonconserved residues were used. Transplanting the cytoplasmic half of either transmembrane segments S5 or S6 from Kv3.1 into Kv2.1 reduced sensitivity to block by internal tetraethylammonium, increased sensitivity to 4-aminopyridine, and reduced single-channel conductance. In S6, changes in single-channel conductance and internal tetraethylammonium sensitivity were associated with point mutations V400T and L403 M, respectively. Although individual residues in both S5 and S6 were found to affect 4-aminopyridine blockade, the most effective change was L327F in S5. Thus, both S5 and S6 contribute to the inner mouth of the pore but different residues regulate ion conduction and blockade by internal tetraethylammonium and 4-aminopyridine.