Dominant-negative subunits reveal potassium channel families that contribute to M-like potassium currents

A A Selyanko; P Delmas; J K Hadley; L Tatulian; I C Wood; M Mistry; B London; D A Brown

doi:10.1523/JNEUROSCI.22-05-j0001.2002

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Dominant-negative subunits reveal potassium channel families that contribute to M-like potassium currents

Journal article

Open access

Peer reviewed

Dominant-negative subunits reveal potassium channel families that contribute to M-like potassium currents

A A Selyanko, P Delmas, J K Hadley, L Tatulian, I C Wood, M Mistry, B London and D A Brown

The Journal of neuroscience, Vol.22(5), pp.RC212-RC212

03/01/2002

DOI: 10.1523/JNEUROSCI.22-05-j0001.2002

PMCID: PMC6758864

PMID: 11880533

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Abstract

M-currents are K+ currents generated by members of the KCNQ family of K+ channels (Wang et al., 1998). However, in some cells, M-like currents may be contaminated by members of other K+ channel gene families, such as the erg family (Meves et al., 1999; Selyanko et al., 1999). In the present experiments, we have used the acute expression of pore-defective mutants of KCNQ3 (DN-KCNQ3) and Merg1a (DN-Merg1a) as dominant negatives to separate the contributions of these two families to M-like currents in NG108-15 neuroblastoma hybrid cells and rat sympathetic neurons. Two kinetically and pharmacologically separable components of M-like current could be recorded from NG108-15 cells that were individually suppressed by DN-Merg1a and DN-KCNQ3, respectively. In contrast, only DN-KCNQ3, and not DN-Merg1a, reduced currents recorded from sympathetic neurons. Pharmacological tests suggested that the residual current in DN-KCNQ3-treated sympathetic neurons was carried by residual KCNQ channels. Ineffectiveness of DN-Merg1a in sympathetic neurons was not caused by lack of expression, as judged by confocal microscopy of Flag-tagged DN-Merg1a. These results accord with previous inferences regarding the roles of erg and KCNQ channels in generating M-like currents. This experimental approach should therefore be useful in delineating the contributions of members of these two gene families to K+ currents in other cells.

Gene Expression

Transfection

Potassium - metabolism

Potassium Channels, Voltage-Gated

Protein Subunits

Multigene Family

Potassium Channels - biosynthesis

Cells, Cultured

Ether-A-Go-Go Potassium Channels

Rats

ERG1 Potassium Channel

Superior Cervical Ganglion - cytology

Rats, Sprague-Dawley

Superior Cervical Ganglion - metabolism

Potassium Channels - genetics

Potassium Channels - metabolism

Patch-Clamp Techniques

Animals

KCNQ3 Potassium Channel

Genes, Dominant

Mice

Neuroblastoma - metabolism

Neurons - metabolism

Hybrid Cells - metabolism

Details

Title: Subtitle: Dominant-negative subunits reveal potassium channel families that contribute to M-like potassium currents
Creators: A A Selyanko - Department of Pharmacology, University College London, London WC1E 6BT, United Kingdom
P Delmas
J K Hadley
L Tatulian
I C Wood
M Mistry
B London
D A Brown
Resource Type: Journal article
Publication Details: The Journal of neuroscience, Vol.22(5), pp.RC212-RC212
Publisher: United States
DOI: 10.1523/JNEUROSCI.22-05-j0001.2002
PMID: 11880533
PMCID: PMC6758864
ISSN: 0270-6474
eISSN: 1529-2401
Grant note: R01HL58030 / NHLBI NIH HHS
Language: English
Date published: 03/01/2002
Academic Unit: Molecular Physiology and Biophysics; Cardiovascular Medicine; Internal Medicine
Record Identifier: 9984025407102771

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