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The Journal of Neuroscience, 2002, 22:RC212:1-5
RAPID COMMUNICATION
Dominant-Negative Subunits Reveal Potassium Channel Families That
Contribute to M-Like Potassium Currents
A. A.
Selyanko1, ,
P.
Delmas1,
J. K.
Hadley1,
L.
Tatulian1,
I. C.
Wood1,
M.
Mistry1,
B.
London2, and
D. A.
Brown1
1 Department of Pharmacology, University College
London, London WC1E 6BT, United Kingdom, and
2 Cardiovascular Institute, University of Pittsburgh
Medical Center, Pittsburgh, Pennsylvania 15213
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.
Key words:
M-current; KCNQ channels; erg channels; dominant
negative; NG108-15 cells; sympathetic neurons
Deceased, September 23, 2001.
Copyright © Society for Neuroscience 0270-6474//$05.00/0
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