Localization of the tandem pore domain K+ channel KCNK5 (TASK-2) in the rat central nervous system

Department of Anesthesia and Operative Intensive Care Medicine, University of Köln, 50924, Köln, Germany.
Molecular Brain Research (Impact Factor: 2). 02/2002; 98(1-2):153-63. DOI: 10.1016/S0169-328X(01)00330-8
Source: PubMed


Tandem pore domain K+ channels (2P K+ channels) are responsible for background K+ currents. 2P K+ channels are the most numerous encoded K+ channels in the Caenorhabditis elegans and Drosophila melanogaster genomes and to date 14 human 2P K+ channels have been identified. The 2P K+ channel TASK-2 (also named KCNK5) is sensitive to changes in extracellular pH, inhibited by local anesthetics and activated by volatile anesthetics. While TASK-1 has been shown to be involved in controlling neuronal cell excitability, much less is known about the cellular expression and function of TASK-2, originally cloned from human kidney. Previous studies demonstrated TASK-2 mRNA expression in high abundance in human kidney, liver, and pancreas, but only low expression in mouse brain or even absent expression in human brain was reported. In this study we have used immunohistochemical methods to localize TASK-2 at the cellular level in the rat central nervous system. TASK-2 immunoreactivity is prominently found in the rat hippocampal formation with the strongest staining observed in the pyramidal cell layer and in the dentate gyrus, and the Purkinje and granule cells of cerebellum. Additional immunofluorescence studies in cultured cerebellar granule cells demonstrate TASK-2 localization to the neuronal soma and to the proximal regions of neurites of cerebellar granule cells. The superficial layers of spinal cord and small-diameter neurons of dorsal root ganglia also showed strong TASK-2 immunoreactivity. These results suggest a possible involvement of TASK-2 in central mechanisms for controlling cell excitability and in peripheral signal transduction.

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Available from: Bruce Winegar, Nov 11, 2014
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    • "mpound 2 in CGN ; however , it was the most active on IKso current , suggesting a possible inhibi - tion over other leak channels . The presence as transcripts of another 4TM / 2P K þ - channels has been reported in CGN : TWIK - 1 , THIK - 2 , TREK - 2 and KCNK - 7 , as high ; TRAAK , TWIK - 2 , TREK - 1 and KCNK - 5 , as low level of expression ( Gabriel et al . , 2002 ; Mathie et al . , 2003 ) . But only TREK - 2 and KCNK - 5 have been functionally characterized and contributed to about 10% and 40% of IKso current , respectively ( Cotten et al . , 2004 ; Han et al . , 2002 ) . 3 . 4 . Effect of organic compounds on the apoptotic cell death of CGN As previously mentioned the TASK channels seemed to be"
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    ABSTRACT: TASK channels belong to the family of K(+) channels with 4 transmembrane segments and 2 pore domains (4TM/2P) per subunit. These channels have been related to apoptosis in cerebellar granule neurons (CGN), as well as cancer in other tissues. TASK current is regulated by hormones, neurotransmitters, anesthetics and divalent cations, which are not selective. Recently, there has been found some organic compounds that inhibit TASK current selectively. In order to find other modulators, we report here a group of five dihydropyrrolo[2,1-a]isoquinolines (DPIs), four of them with putative anticancer activity, that were evaluated on TASK-1 and TASK-3 channels. The compounds 1, 2 and 3 showed IC50 <320 μM on TASK-1 and TASK-3, intermediate activity on TASK-1/TASK-3 heterodimer, moderate effect over hslo and TREK-1 (500 μM), and practically not inhibition on Shaker-IR, herg and IRK2.1 potassium channels, when they were expressed heterologously in Xenopus laevis oocytes. In rat CGN, 500 μM of these three compounds induced a decrement by >39% of the TASK-carried leak current. Finally, only compound 1 showed significant protection (∼36%) against apoptotic death of CGN induced by K(+) deprivation. These results suggest that DPI compounds could be potential candidates for designing new selective inhibitors of TASK channels.
    Neuropharmacology 11/2013; 79. DOI:10.1016/j.neuropharm.2013.10.028 · 5.11 Impact Factor
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    • "TASK-1 has been detected in small-to medium-diameter DRG cell types and it has been proposed that these sensory afferents might contain functional heterodimeric channels (Rau et al., 2006). In the spinal cord, strong TASK-1 immunoreactivity has been mainly reported in ependymal cells lining the central canal and in white matter (Kindler et al., 2000). d. "
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    ABSTRACT: The endocannabinoid system has emerged during the last two decades as a very important regulator of neuronal and cellular activity in many different body tissues and particularly in the central and peripheral nervous systems. The endocannabinoid system constitutes of lipid signaling molecules (the endocannabinoids), the enzymatic machineries for their synthesis and degradation, and their cellular targets, the cannabinoid receptors. “Bona fide” targets of endocannabinoids are the G protein-coupled cannabinoid receptors type 1 and type 2 (CB1 and CB2 receptors, respectively). However, recent evidence indicates that endocannabinoids also have other targets besides “classical” cannabinoid receptors. Furthermore, the steadily growing list of newly discovered elements of endocannabinoid signaling further expands the definition of the endocannabinoid system on an almost daily base. In this chapter, we will describe the anatomical distribution of the various elements of the endocannabinoid system in the brain, the spinal cord and the peripheral nervous system. In particular, we will address the distribution of receptors (CB1 and CB2 receptors and other targets of endocannabinoids), of enzymes involved in the synthesis and degradation of endocannabinoids, and of the two major endocannabinoids described so far, anandamide and 2-arachidonoyl-glycerol. Particular emphasis will be given to new findings indicating a larger distribution of the endocannabinoid system in nervous tissues than previously believed. The need for improvement of unbiased techniques for the detection of various elements of the endocannabinoid system will be also underlined, which will allow a more precise identification of the sites where endocannabinoid signalling exerts important physiological and pathophysiological functions.
    Cannabinoids and the Brain, 12/2007: pages 161-201;
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    ABSTRACT: K+channels TASK1and 2 in relation to gestationand differentiation, usingvilloustissuefromfirst and third trimester andcultured cytotrophoblast cells atmononucleate andmultinucleate stages ofculture. METHODS: Quantitative real-time polymerase chain reaction (PCR), immunofluorescence, and86Rb+ (K)eftiux wereused toinvestigate TASKchannel expression andfunction. RESULTS:TASK2mRNA expression washigher infirst trimester than term(10to13vs38to40weeks, P
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