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© The Rockefeller University Press, 0022-1295/1998//651/ $5.00
Journal of General Physiology, Volume 112, Number 6, 1998

Article

Single-Channel Characteristics of Wild-Type IKs Channels and Channels formed with Two MinK Mutants that Cause Long QT Syndrome

Federico Sesti and Steve A.N. Goldstein

From the Section of Developmental Biology and Biophysics, Departments of Pediatrics and Cellular and Molecular Physiology, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06536-0812

IKs channels are voltage dependent and K+ selective. They influence cardiac action potential duration through their contribution to myocyte repolarization. Assembled from minK and KvLQT1 subunits, IKs channels are notable for a heteromeric ion conduction pathway in which both subunit types contribute to pore formation. This study was undertaken to assess the effects of minK on pore function. We first characterized the properties of wild-type human IKs channels and channels formed only of KvLQT1 subunits. Channels were expressed in Xenopus laevis oocytes or Chinese hamster ovary cells and currents recorded in excised membrane patches or whole-cell mode. Unitary conductance estimates were dependent on bandwidth due to rapid channel "flicker." At 25 kHz in symmetrical 100-mM KCl, the single-channel conductance of IKs channels was ~16 pS (corresponding to ~0.8 pA at 50 mV) as judged by noise-variance analysis; this was fourfold greater than the estimated conductance of homomeric KvLQT1 channels. Mutant IKs channels formed with D76N and S74L minK subunits are associated with long QT syndrome. When compared with wild type, mutant channels showed lower unitary currents and diminished open probabilities with only minor changes in ion permeabilities. Apparently, the mutations altered single-channel currents at a site in the pore distinct from the ion selectivity apparatus. Patients carrying these mutant minK genes are expected to manifest decreased K+ flux through IKs channels due to lowered single-channel conductance and altered gating.

Key Words: KvLQT1 • heart • potassium • long QT syndrome • delayed rectifier

Address correspondence to Steve A.N. Goldstein, Section of Developmental Biology and Biophysics, Departments of Pediatrics and Cellular and Molecular Physiology, Boyer Center for Molecular Medicine, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536-0812. Fax: 203-737-2290; E-mail: steve.goldstein{at}yale.edu

Abbreviations: CHO, Chinese hamster ovary; LQTS, long QT syndrome


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Y. Yang and F. J. Sigworth
Single-Channel Properties of IKs Potassium Channels
J. Gen. Physiol., December 1, 1998; 112(6): 665 - 678.
[Abstract] [Full Text] [PDF]


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