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A comparison of currents carried by HERG, with and without coexpression of MiRP1, and the native rapid delayed rectifier current. Is MiRP1 the missing link?

Authors
Type
Published Article
Journal
The Journal of physiology
Publication Date
Volume
540
Issue
Pt 1
Pages
15–27
Identifiers
PMID: 11927665
Source
Medline
License
Unknown

Abstract

Although it has been suggested that coexpression of minK related peptide (MiRP1) is required for reconstitution of native rapid delayed-rectifier current (I(Kr)) by human ether-a-go-go related gene (HERG), currents resulting from HERG (I(HERG)) and HERG plus MiRP1 expression have not been directly compared with native I(Kr). We compared the pharmacological and selected biophysical properties of I(HERG) with and without MiRP1 coexpression in Chinese hamster ovary (CHO) cells with those of guinea-pig I(Kr) under comparable conditions. Comparisons were also made with HERG expressed in Xenopus oocytes. MiRP1 coexpression significantly accelerated I(HERG) deactivation at potentials negative to the reversal potential, but did not affect more physiologically relevant deactivation of outward I(HERG), which remained slower than that of I(Kr). MiRP1 shifted I(HERG) activation voltage dependence in the hyperpolarizing direction, whereas I(Kr) activated at voltages more positive than I(HERG). There were major discrepancies between the sensitivity to quinidine, E-4031 and dofetilide of I(HERG) in Xenopus oocytes compared to I(Kr), which were not substantially affected by coexpression with MiRP1. On the other hand, the pharmacological sensitivity of I(HERG) in CHO cells was indistinguishable from that of I(Kr) and was unaffected by MiRP1 coexpression. We conclude that the properties of I(HERG) in CHO cells are similar in many ways to those of native I(Kr) under the same recording conditions, and that the discrepancies that remain are not reduced by coexpression with MiRP1. These results suggest that the physiological role of MiRP1 may not be to act as an essential consituent of the HERG channel complex carrying native I(Kr).

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