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Science 15 September 2000:
Vol. 289. no. 5486, pp. 1942 - 1946
DOI: 10.1126/science.289.5486.1942
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Reports

Respiration and Parturition Affected by Conditional Overexpression of the Ca2+-Activated K+ Channel Subunit, SK3

Chris T. Bond,1 Rolf Sprengel,6 John M. Bissonnette,2 Walter A. Kaufmann,5 David Pribnow,3 Torben Neelands,1 Thorsten Storck,6 Manfred Baetscher,4 Jasna Jerecic,6 James Maylie,2 Hans-Günther Knaus,5 Peter H. Seeburg,6 John P. Adelman1*

In excitable cells, small-conductance Ca2+-activated potassium channels (SK channels) are responsible for the slow after-hyperpolarization that often follows an action potential. Three SK channel subunits have been molecularly characterized. The SK3 gene was targeted by homologous recombination for the insertion of a gene switch that permitted experimental regulation of SK3 expression while retaining normal SK3 promoter function. An absence of SK3 did not present overt phenotypic consequences. However, SK3 overexpression induced abnormal respiratory responses to hypoxia and compromised parturition. Both conditions were corrected by silencing the gene. The results implicate SK3 channels as potential therapeutic targets for disorders such as sleep apnea or sudden infant death syndrome and for regulating uterine contractions during labor.

1 Vollum Institute,
2 Department of Obstetrics and Gynecology,
3 Department of Cell and Developmental Biology,
4 Department of Molecular and Medical Genetics, Oregon Health Sciences University, Portland, OR 97201, USA.
5 Institute of Biochemical Pharmacology, University of Innsbruck, A-6020 Innsbruck/Tyrol, Austria.
6 Department of Molecular Neuroscience, Max-Planck-Institute for Medical Research, D-69120 Heidelberg, Germany.
*   To whom correspondence should be addressed. E-mail: adelman{at}ohsu.edu

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Science. ISSN 0036-8075 (print), 1095-9203 (online)