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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, dagger , 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


dagger Deceased, September 23, 2001.


Copyright © Society for Neuroscience  0270-6474//$05.00/0


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