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(Circulation Research. 2001;88:981.)
© 2001 American Heart Association, Inc.

Editorial

Do All Voltage-Gated Potassium Channels Use MiRPs?

Geoffrey W. Abbott, Steve A. N. Goldstein, Federico Sesti

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, Conn.

Correspondence to Steve A.N. Goldstein, 295 Congress Ave, New Haven, CT 06536. E-mail steve.goldstein@yale.edu

Key Words: potassium channels • KCNE2 • MiRP1 • I_Kr • I_to

	Introduction

 
Once again, a MinK-related peptide (MiRP) has been implicated in allowing a pore-forming, voltage-gated potassium channel subunit to achieve its potential. In this issue of Circulation Research, Zhang et al¹ show that MiRP1 (encoded by the KCNE2 gene) can alter the function of Kv4 family subunits (which contribute to I_to, transient outward currents in heart and brain) when they are expressed together in Xenopus oocytes. After recent reports that MiRP1 affects the behavior of HERG^{2 3 4 5 6} and MiRP2 affects the function of KCNQ1, KCNQ4, HERG, and Kv3.4,^{7 8} the MiRP subunits have been accused of widespread promiscuous partnering. Whether this salacious charge is a valid reflection of natural physiology is the critical issue at hand.

MinK and its four recognized relations (MiRP1 through MiRP4 encoded by KCNE1 through KCNE5) are diminutive single-transmembrane subunits that coassemble with subunits during protein translation to form stable complexes^{9 10} (Figure). In doing so, MinK alters the gating kinetics, permeation attributes, and pharmacology of KCNQ1 subunits to yield the attributes recorded for native cardiac I_Ks channels.^{11 12} So, too, MiRP1 and HERG combine to create complexes with unique functions that recapitulate the properties of cardiac I_Kr channels.^{2 3 4 5 6} In each of these cases, inherited mutations in either the MiRP or its associated subunit partner have been linked to similar pathophysiology. The present work by Zhang et al¹ indicates that MiRP1 can alter the function of Kv4 subunits in experimental cells and demands we consider the possibility that MiRP subunits play a central role in determining cardiovascular . . . [Full Text of this Article]

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