Functional coassembly of KCNQ4 with KCNE-β-subunits in Xenopus oocytes

Nathalie Strutz-Seebohm, Guiscard Seebohm, Olga Fedorenko, Ravshan Baltaev, Jutta Engel, Martina Knirsch, Florian Lang

Research output: Contribution to journalArticle

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Abstract

The KCNQ gene family comprises voltage-gated potassium channels expressed in epithelial tissues (KCNQ1, KCNQ5), inner ear structures (KCNQ1, KCNQ4) and the brain (KCNQ2-5). KCNQ4 is expressed in inner and outer hair cells of the inner ear where it influences electrical excitability and cell survival. Accordingly, loss of function mutations of the KCNQ4 gene cause hearing loss in humans and functional k.o.-mice show progressive degeneration of outer hair cells (OHCs). However, characteristic electrophysiological features of the native KCNQ4-carried current IK,n in OHCs are not recapitulated by expression of KCNQ4 channels in heterologous expression systems. This might suggest modulation of KCNQ4 by interacting KCNE β-subunits, which are known to modify the properties of the closely related KCNQ1. The present study explored whether transcripts of the KCNE isoforms could be identified in OHC mRNA and whether the subunits modulate KCNQ4 function. RT-PCR indeed yielded transcripts of all five KCNEs in OHCs. Coexpression of the KCNE-β-subunits with human KCNQ4 in the Xenopus laevis oocyte expression system revealed that all KCNEs modulate KCNQ4 voltage dependence, protein stability and ion selectivity of hKCNQ4 in Xenopus oocytes. The deafness-associated Jervell and Lange-Nielsen syndrome (JLNS) mutation KCNE1(D76N) impairs KCNQ4-function whereas the Romano-Ward syndrome (RWS) mutant KCNE1(S74L), which shows normal hearing in patients, does not impair KCNQ4 channel function. In conclusion, KCNEs are presumably coexpressed with KCNQ4 in hair cells from the organ of Corti and might regulate KCNQ4 functional properties, effects that could be important under physiological and pathophysiological conditions.

Original languageEnglish
Pages (from-to)57-66
Number of pages10
JournalCellular Physiology and Biochemistry
Volume18
Issue number1-3
DOIs
Publication statusPublished - 1 Jan 2006

Fingerprint

Outer Auditory Hair Cells
Xenopus
Oocytes
Inner Ear
Inner Auditory Hair Cells
Jervell-Lange Nielsen Syndrome
Romano-Ward Syndrome
Voltage-Gated Potassium Channels
Organ of Corti
Mutation
Protein Stability
Xenopus laevis
Deafness
Hearing Loss
Hearing
Genes
Cell Survival
Protein Isoforms
Epithelium
Ions

Keywords

  • Channel kinetics
  • Gating Kv7
  • Kinase
  • MinK
  • Mirp

ASJC Scopus subject areas

  • Physiology

Cite this

Strutz-Seebohm, N., Seebohm, G., Fedorenko, O., Baltaev, R., Engel, J., Knirsch, M., & Lang, F. (2006). Functional coassembly of KCNQ4 with KCNE-β-subunits in Xenopus oocytes. Cellular Physiology and Biochemistry, 18(1-3), 57-66. https://doi.org/10.1159/000095158

Functional coassembly of KCNQ4 with KCNE-β-subunits in Xenopus oocytes. / Strutz-Seebohm, Nathalie; Seebohm, Guiscard; Fedorenko, Olga; Baltaev, Ravshan; Engel, Jutta; Knirsch, Martina; Lang, Florian.

In: Cellular Physiology and Biochemistry, Vol. 18, No. 1-3, 01.01.2006, p. 57-66.

Research output: Contribution to journalArticle

Strutz-Seebohm, N, Seebohm, G, Fedorenko, O, Baltaev, R, Engel, J, Knirsch, M & Lang, F 2006, 'Functional coassembly of KCNQ4 with KCNE-β-subunits in Xenopus oocytes', Cellular Physiology and Biochemistry, vol. 18, no. 1-3, pp. 57-66. https://doi.org/10.1159/000095158
Strutz-Seebohm, Nathalie ; Seebohm, Guiscard ; Fedorenko, Olga ; Baltaev, Ravshan ; Engel, Jutta ; Knirsch, Martina ; Lang, Florian. / Functional coassembly of KCNQ4 with KCNE-β-subunits in Xenopus oocytes. In: Cellular Physiology and Biochemistry. 2006 ; Vol. 18, No. 1-3. pp. 57-66.
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