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          Institute: MPI für medizinische Forschung     Collection: Abteilung Molekulare Neurobiologie     Display Documents

ID: 22841.0, MPI für medizinische Forschung / Abteilung Molekulare Neurobiologie
Respiration and parturition affected by conditional overexpression of the Ca2+ -activated K+ channel subunit, SK3
Translation of Title:Respiration and parturition affected by conditional overexpression of the Ca<sup>2+</sup> -activated K<sup>+</sup> channel subunit, SK3
Authors:Bond, Chris T.; Sprengel, Rolf; Bissonnette, John M.; Kaufmann, Walter A.; Pribnow, David; Neelands, Torben; Storck, Thorsten; Baetscher, Manfred; Jerecic, Jasna; Maylie, James; Knaus, Hans-Günther; Seeburg, Peter H.; Adelman, John P.
Date of Publication (YYYY-MM-DD):2000-09-15
Title of Journal:Science
Journal Abbrev.:Science
Issue / Number:5486
Start Page:1942
End Page:1946
Review Status:Peer-review
Audience:Experts Only
Intended Educational Use:No
Abstract / Description: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. SK channels are potassium-selective, voltage-independent, and activated by increases in the levels of intracellular Ca2+, such as what occurs during an action potential (1, 2). We have characterized three mammalian SK subunits (hSK1, rSK2, and rSK3) by molecular cloning. All three form SK channels with similar Ca2+ sensitivity and gating kinetics; constitutive association of calmodulin accomplishes Ca2+ gating with an intracellular domain of the channel alpha subunits (3, 4). To investigate the physiological role of murine SK3, we site-specifically inserted a tetracycline-based genetic switch into the 5 untranslated region of the gene so that subunit expression could be abolished by dietary doxycycline (dox) administration without interfering with the normal profile of SK3 expression.
External Publication Status:published
Document Type:Article
Communicated by:Wulf Kaiser
Affiliations:MPI für medizinische Forschung/Abteilung Molekulare Neurobiologie/
Identifiers:URI:http://www.sciencemag.org/cgi/content/full/289/548... [Full text]
URI:http://www.sciencemag.org/cgi/content/abstract/289... [Abstract]
URI:http://www.sciencemag.org/cgi/reprint/289/5486/194... [Fulltext PDF]
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