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This Article Full Text Full Text (PDF) All Versions of this Article: 290/3/H1038    most recent 00679.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Zhang, S. Search for Related Content PubMed PubMed Citation Articles by Zhang, S.

Isolation and characterization of I_Kr in cardiac myocytes by Cs⁺ permeation

Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, and Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada

Submitted 22 June 2005 ; accepted in final form 8 October 2005

Isolation of the rapidly activating delayed rectifier potassium current (I_Kr) from other cardiac currents has been a difficult task for quantitative study of this current. The present study was designed to separate I_Kr using Cs⁺ in cardiac myocytes. Cs⁺ have been known to block a variety of K⁺ channels, including many of those involved in the cardiac action potential such as inward rectifier potassium current I_K1 and the transient outward potassium current I_to. However, under isotonic Cs⁺ conditions (135 mM Cs⁺), a significant membrane current was recorded in isolated rabbit ventricular myocytes. This current displayed the voltage-dependent onset of and recovery from inactivation that are characteristic to I_Kr. Consistently, the current was selectively inhibited by the specific I_Kr blockers. The biophysical and pharmacological properties of the Cs⁺-carried human ether-a-go-go-related gene (hERG) current were very similar to those of the Cs⁺-carried I_Kr in ventricular myocytes. The primary sequence of the selectivity filter in hERG was in part responsible for the Cs⁺ permeability, which was lost when the sequence was changed from GFG to GYG, characteristic of other, Cs⁺-impermeable K⁺ channels. Thus the unique high Cs⁺ permeability in I_Kr channels provides an effective way to isolate I_Kr current. Although the biophysical and pharmacological properties of the Cs⁺-carried I_Kr are different from those of the K⁺-carried I_Kr, such an assay enables I_Kr current to be recorded at a level that is large enough and sufficiently robust to evaluate any I_Kr alterations in native tissues in response to physiological or pathological changes. It is particularly useful for exploring the role of reduction of I_Kr in arrhythmias associated with heart failure and long QT syndrome due to the reduced hERG channel membrane expression.

cesium; rapidly activating delayed rectifier potassium current; potassium channel; human ether-a-go-go-related gene; patch clamp