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This Article Full Text Full Text (PDF) All Versions of this Article: 585/3/867    most recent jphysiol.2007.145649v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dobler, T. Articles by Döring, F. Search for Related Content PubMed PubMed Citation Articles by Dobler, T. Articles by Döring, F. Related Collections Neuroscience

¹ Institute of Physiology, University of Würzburg, 97070 Würzburg, Germany
² Clinical and Molecular Psychobiology, Department of Psychiatry and Psychotherapy, University of Würzburg, 97080 Würzburg, Germany
³ Ingenium Pharmaceuticals AG, 82152 Martinsried, Germany

TRESK (TWIK-related spinal cord K⁺ channel) is the most recently identified member of the two-pore-domain potassium channel (K_2P) family, the molecular source of background potassium currents. Human TRESK channels are not affected by external acidification. However, the mouse orthologue displays moderate pH dependence isolated to a single histidine residue adjacent to the GYG selectivity filter. In the human protein, sequence substitution of tyrosine by histidine at this critical position generated a mutant that displays almost identical proton sensitivity compared with mouse TRESK. In contrast to human TRESK, which is specifically located in spinal cord, we detected mouse TRESK (mTRESK) mRNA in several epithelial and neuronal tissues including lung, liver, kidney, brain and spinal cord. As revealed by endpoint and quantitative RT-PCR, mTRESK channels are mainly expressed in dorsal root ganglia (DRG) and on the transcript level represent the most important background potassium channel in this tissue. DRG neurones of all sizes were labelled by in situ hybridizations with TRESK-specific probes. In DRG neurones of TRESK[G339R] functional knock-out (KO) mice the standing outward current IK_so was significantly reduced compared with TRESK wild-type (WT) littermates. Different responses to K_2P channel regulators such as bupivacaine, extracellular protons and quinidine corroborated the finding that approximately 20% of IK_so is carried by TRESK channels. Unexpectedly, we found no difference in resting membrane potential between DRG neurones of TRESK[WT] and TRESK[G339R] functional KO mice. However, in current-clamp recordings we observed significant changes in action potential duration and amplitude of after-hyperpolarization. Most strikingly, cellular excitability of DRG neurones from functional KO mice was significantly augmented as revealed by reduced rheobase current to elicit action potentials.

(Received 27 September 2007; accepted after revision 22 October 2007; first published online 25 October 2007)
Corresponding author E. Wischmeyer: Institute of Physiology, University of Würzburg, Röntgenring 9, 97070 Würzburg, Germany. Email: e.wischmeyer{at}mail.uni-wuerzburg.de

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