KCNE1 reverses the response of the human K+ channel KCNQ1 to cytosolic pH changes and alters its pharmacology and sensitivity to temperature.

Détails

ID Serval
serval:BIB_8DD8E3455F5A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
KCNE1 reverses the response of the human K+ channel KCNQ1 to cytosolic pH changes and alters its pharmacology and sensitivity to temperature.
Périodique
Pflügers Archiv : European Journal of Physiology
Auteur(s)
Unsöld B., Kerst G., Brousos H., Hübner M., Schreiber R., Nitschke R., Greger R., Bleich M.
ISSN
0031-6768 (Print)
ISSN-L
0031-6768
Statut éditorial
Publié
Date de publication
2000
Peer-reviewed
Oui
Volume
441
Numéro
2-3
Pages
368-378
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
Previous studies have shown that heteromultimeric KCNQ1/KCNE1 (KvLQT1/minK) channels and homomultimeric KCNQ1 (KvLQT1) channels exhibit different current properties, e.g. distinct kinetics and different sensitivities to drugs. In this study we report on the divergent responses to internal pH changes and further characterize some of the current properties of the human isoforms of KCNQ1 and KCNE1 expressed in Chinese hamster ovary (CHO) cells or Xenopus laevis oocytes. Decreasing the bath temperature from 37 degrees C to 20 degrees C increased the half-activation time by a factor of 5 for KCNQ1/KCNE1 currents (IKs) but by only twofold (not significant) for KCNQ1 currents (IK) in CHO cells. Acidification of cytosolic pH (pHi) increased IKs but decreased 1K whereas intracellular alkalinization decreased I(Ks) but increased IK. pHi-induced changes in intracellular Ca2+ activity ([Ca2+]i) did not correlate with the current responses. At 20 degrees C mefenamic acid (0.1 mM) significantly augmented IKs but slightly decreased IK. It changed the slow activation kinetics of I(Ks) to an instantaneous onset. The form of the current/voltage (I/V) curve changed from sigmoidal to almost linear. In contrast, at 37 degrees C, mefenamic acid also increased I(Ks) but slowed the activation kinetics and shifted the voltage activation to more hyperpolarized values without markedly affecting the sigmoidal shape of the I/V curve. The potassium channel blockers clotrimazole and tetrapentylammonium (TPeA) inhibited I(Ks) with a lower potency than I(K). These results show that coexpression of KCNE1 reversed pH regulation of KCNQ1 from inhibition to activation by acidic pHi. In addition, KCNE1 altered the pharmacological properties and sensitivity to temperature of KCNQ1. The pH-dependence of I(Ks) might be of clinical and pathophysiological relevance in the pathogenesis of ischaemic cardiac arrhythmias.
Mots-clé
Animals, Buffers, CHO Cells, Clotrimazole/pharmacology, Cricetinae, Cytosol/chemistry, Electric Conductivity, Gene Expression, Humans, Hydrogen-Ion Concentration, KCNQ Potassium Channels, KCNQ1 Potassium Channel, Kinetics, Mefenamic Acid/pharmacology, Potassium Channel Blockers, Potassium Channels/drug effects, Potassium Channels/genetics, Potassium Channels, Voltage-Gated, Quaternary Ammonium Compounds/pharmacology, Temperature, Transfection
Pubmed
Web of science
Création de la notice
05/08/2012 12:23
Dernière modification de la notice
03/03/2018 19:17
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