Pore helix domain charged residues modulate inactivation of the hERG K+ channel

Ju, P, Torres, AM, Bansal, PS, Kuchel, PW and Vandenberg, JI (2007) Pore helix domain charged residues modulate inactivation of the hERG K+ channel. Biophysical Journal: 2007 BPS Annual Meeting Abstracts, Supplement: 123A-123A.

Author Ju, P
Torres, AM
Bansal, PS
Kuchel, PW
Vandenberg, JI
Title Pore helix domain charged residues modulate inactivation of the hERG K+ channel
Journal name Biophysical Journal: 2007 BPS Annual Meeting Abstracts   Check publisher's open access policy
ISSN 0006-3495
Publication date 2007-01-01
Year available 2007
Sub-type Published abstract
Issue Supplement
Start page 123A
End page 123A
Total pages 1
Place of publication Bethesda
Publisher Biophysical Society
Language eng
Abstract Potassium ion channels encoded by the human ether-a-go-go-related gene (hERG) have very unusual kinetic behavior, characterized by slow activation but very rapid inactivation. The unusually rapid inactivation of the channel, relative to the rate of its activation, is crucial for normal cardiac repolarization and suppression of propagation of premature beats. Inactivation of the hERG K+ channel results from conformational changes in its outer pore domain. We used a combination of NMR spectroscopy, site-directed mutagenesis and electrophysiology to probe the molecular basis of inactivation of hERG K+ channels. Our NMR studies of the outer pore domain showed that the pore helix domain of the channel extends significantly further into the extracellular space than the homologous domain in the K+ channels, for which crystal structures are known. It is interesting to note that the extension of the hERG pore helix, which includes K608, D609 and K610 residues, is highly charged. In addition, the KDK motif of hERG is not conservative even within the “EAG” subfamily of voltage-gated K+ channels. Our electrophysiological studies, in combination with site-directed mutagenesis, showed that both the charge, and helical content of the KDK motif are important for the kinetics and voltage-dependence of inactivation in hERG channels. These studies highlight the importance of the unique structural elements in the outer pore domain for the unusual inactivation kinetics of hERG K+ channels.
Keyword Biophysics
Q-Index Code CX
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Published abstract
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Created: Tue, 19 Feb 2008, 02:12:24 EST