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A constitutively open potassium channel formed by KCNQ1 and KCNE3

Abstract

Mutations in all four known KCNQ potassium channel α-subunit genes lead to human diseases1,2,3,4,5,6. KCNQ1 (KvLQT1)1 interacts with the β-subunit KCNE1 (IsK, minK)7 to form the slow, depolarization-activated potassium current IKs8,9 that is affected in some forms of cardiac arrhythmia. Here we show that the novel β-subunit KCNE3 markedly changes KCNQ1 properties to yield currents that are nearly instantaneous and depend linearly on voltage. It also suppresses the currents of KCNQ4 and HERG potassium channels. In the intestine, KCNQ1 and KCNE3 messenger RNAs colocalized in crypt cells. This localization and the pharmacology, voltage-dependence and stimulation by cyclic AMP of KCNQ1/KCNE3 currents indicate that these proteins may assemble to form the potassium channel that is important for cyclic AMP-stimulated intestinal chloride secretion and that is involved in secretory diarrhoea and cystic fibrosis.

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Figure 1: Primary structure of KCNE3.
Figure 2: Modification of KCNQ1 currents by KCNE1 and KCNE3.
Figure 3: Stimulation of KCNE3 surface expression by KCNQ1.
Figure 4: Effect of KCNE3 on other channels.
Figure 5: Chromanol 293B-sensitive currents in rat colonic crypt cells.
Figure 6: Localization of KCNQ1 and KCNE3 in the mouse small intestine and colon by in situ hybridization.

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Acknowledgements

We thank J. P. Hardelin and C. Petit for performing KCNE3 in situ hybridization of cochlear sections. This work was supported by grants from the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen Industrie to R.G. and T.J.J.

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Correspondence to Thomas J. Jentsch.

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Schroeder, B., Waldegger, S., Fehr, S. et al. A constitutively open potassium channel formed by KCNQ1 and KCNE3. Nature 403, 196–199 (2000). https://doi.org/10.1038/35003200

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