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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?

A comparison of currents carried by HERG, with and without coexpression of MiRP1, and the native... Although it has been suggested that coexpression of minK related peptide (MiRP1) is required for reconstitution of native rapid delayed‐rectifier current (IKr) by human ether‐a‐go‐go related gene (HERG), currents resulting from HERG (IHERG) and HERG plus MiRP1 expression have not been directly compared with native IKr. We compared the pharmacological and selected biophysical properties of IHERG with and without MiRP1 coexpression in Chinese hamster ovary (CHO) cells with those of guinea‐pig IKr under comparable conditions. Comparisons were also made with HERG expressed in Xenopus oocytes. MiRP1 coexpression significantly accelerated IHERG deactivation at potentials negative to the reversal potential, but did not affect more physiologically relevant deactivation of outward IHERG, which remained slower than that of IKr. MiRP1 shifted IHERG activation voltage dependence in the hyperpolarizing direction, whereas IKr activated at voltages more positive than IHERG. There were major discrepancies between the sensitivity to quinidine, E‐4031 and dofetilide of IHERG in Xenopus oocytes compared to IKr, which were not substantially affected by coexpression with MiRP1. On the other hand, the pharmacological sensitivity of IHERG in CHO cells was indistinguishable from that of IKr and was unaffected by MiRP1 coexpression. We conclude that the properties of IHERG in CHO cells are similar in many ways to those of native IKr 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 IKr. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Physiology Wiley

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?

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References (28)

Publisher
Wiley
Copyright
Copyright © 2002 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0022-3751
eISSN
1469-7793
DOI
10.1113/jphysiol.2001.013296
Publisher site
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Abstract

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

Journal

The Journal of Physiology – Wiley

Published: Apr 1, 2002

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