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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?
J Physiol. 2002 Apr 01; 540(Pt 1):15-27.JP

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).

Authors+Show Affiliations

Research Center, Montreal Heart Institute, Department of Pharmacology and Therapeutics, McGill University, Quebec, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11927665

Citation

Weerapura, Manjula, et al. "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?" The Journal of Physiology, vol. 540, no. Pt 1, 2002, pp. 15-27.
Weerapura M, Nattel S, Chartier D, et al. 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? J Physiol. 2002;540(Pt 1):15-27.
Weerapura, M., Nattel, S., Chartier, D., Caballero, R., & Hébert, T. E. (2002). 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? The Journal of Physiology, 540(Pt 1), 15-27.
Weerapura M, et al. 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. J Physiol. 2002 Apr 1;540(Pt 1):15-27. PubMed PMID: 11927665.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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? AU - Weerapura,Manjula, AU - Nattel,Stanley, AU - Chartier,Denis, AU - Caballero,Ricardo, AU - Hébert,Terence E, PY - 2002/4/3/pubmed PY - 2002/9/24/medline PY - 2002/4/3/entrez SP - 15 EP - 27 JF - The Journal of physiology JO - J Physiol VL - 540 IS - Pt 1 N2 - 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). SN - 0022-3751 UR - https://www.unboundmedicine.com/medline/citation/11927665/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 DB - PRIME DP - Unbound Medicine ER -