Differential distribution of TASK-1, TASK-2 and TASK-3 immunoreactivities in the rat and human cerebellum

Rusznák, Zoltán; Pocsai, Krisztina; Kovács, Ilona; Pór, Ágnes; Pál, Balázs; Bı́ró, Tamás; Szücs, G

doi:10.1007/s00018-004-4082-3

Cited by 34 publications

(28 citation statements)

References 45 publications

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“…The expression of the four subunits in large cells was not greatly influenced by deafening, which predominantly decreased their expression in small and medium sized cells. K 2p channel subunits have been previously identified in astrocytes (Gnatenco et al, 2002;Rusznak et al, 2004, Kindler et al, 2000 where they have been suggested to play a role in ionic homeostasis. Skatchkov et al (2006) reported that K 2p channel subunits are functionally expressed in retinal glial cells.…”

Section: Discussionmentioning

confidence: 99%

Deafness associated changes in two-pore domain potassium channels in the rat inferior colliculus

et al. 2007

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Two-pore potassium channels can influence neuronal excitability by regulating background leakage of potassium ions and resting membrane potential. The present study used quantitative real time PCR and in situ hybridization to determine if the decreased activity from deafness would induce changes in two-pore potassium channel subunit expression in the rat inferior colliculus. Ten subunits were assessed with qRT-PCR at 3 days, 3 weeks and 3 months following bilateral cochlear ablation. TASK-1, TASK-5 and THIK-2 showed significant decreases in expression at all three times assessed. TASK-5, relatively specific to auditory neurons, had the greatest decrease. TWIK-1 was significantly decreased at 3 weeks and 3 months following deafness and TREK-2 was only significantly decreased at 3 days. TASK-3, TWIK-2, THIK-1, TRAAK and TREK-1 did not show any significant changes in gene expression. In situ hybridization was used to examine TASK-1, TASK-5, TWIK-1 and THIK-2 in the central nucleus, dorsal cortex and lateral (external) cortex of the IC in normal hearing animals and at 3 weeks following deafening. All four subunits showed expression in neurons throughout IC subdivisions in normal hearing rats, with TASK-5 having the greatest overall number of labeled neurons. There was no co-localization of subunit expression with GFAP immunostaining, indicating no expression in glia. Three weeks following deafening there was a significant decrease in the number of neurons expressing TASK-1 and THIK-2 in the IC, while TASK-5 had significant decreases in the central nucleus and dorsal cortex and TWIK-1 in the lateral and dorsal cortices. Two-pore potassium channels (K 2p ) are a class of open rectifying potassium selective channels (Ketchum et al., 1995) that, when activated, allow a background leakage of potassium ions that raises the resting membrane potential to hyperpolarizing levels, resulting in decreased neuronal excitability (see Lesage and Lazdunski, 2000;Goldstein et al., 2001;Patel and Honore, 2001; Plant et al., 2005 for reviews). There are, to date, 18 subunits in the K 2p channel family that have been divided into different classes based on what is know about their sensitivities. The TASK-1 (K 2p 3.1, KCNK3), TASK-3 (K 2p 9.1, KCNK9) and TWIK-1 (K 2p 1.1, KCNK1) subunits are widely expressed throughout the brain but have been reported to have only moderate expression in the auditory brain stem Talley et al., 2001). The TASK-5 (K 2p 15.1, KCNK15) subunit has a relatively selective expression, primarily found in Author for correspondence: Dr. Richard A. Altschuler, KHRI, Department of Otolaryngology, The University of Michigan, 1301 East Ann Street, Ann Arbor, MI, Tel: (734) Fax: (734) 764-0014, E-mail: E-mail: shuler@umich.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof befo...

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Section: Discussionmentioning

confidence: 99%

Deafness associated changes in two-pore domain potassium channels in the rat inferior colliculus

et al. 2007

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“…Astrocytes of hippocampus and cerebellum express TASK1 protein (Kindler et al, 2000;Millar et al, 2000;Kanjhan et al, 2004;Rusznak et al, 2004;Kim et al, 2007), but so far evidence of functional expression of acidand bupivacaine-sensitive TASK channels in these cells is lacking. The present study also failed at finding effects of bupivacaine after inhibiting Kir-and 4-AP-sensitive voltage-gated currents.…”

Section: Expression Of K 2p Channels By Hippocampal Astrocytesmentioning

confidence: 99%

Analysis of Astroglial K+ Channel Expression in the Developing Hippocampus Reveals a Predominant Role of the Kir4.1 Subunit

Seifert¹,

Hüttmann²,

Binder³

et al. 2009

Journal of Neuroscience

200

226

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Astrocytes in different brain regions display variable functional properties. In the hippocampus, astrocytes predominantly express timeand voltage-independent currents, but the underlying ion channels are not well defined. This ignorance is partly attributable to abundant intercellular coupling of these cells through gap junctions, impeding quantitative analyses of intrinsic membrane properties. Moreover, distinct types of cells with astroglial properties coexist in a given brain area, a finding that confused previous analyses. In the present study, we investigated expression of inwardly rectifying (Kir) and two-pore-domain (K 2P ) K ϩ channels in astrocytes, which are thought to be instrumental in the regulation of K ϩ homeostasis. Freshly isolated astrocytes were used to improve space-clamp conditions and allow for quantitative assessment of functional parameters. Patch-clamp recordings were combined with immunocytochemistry, Western blot analysis, and semiquantitative transcript analysis. Comparative measurements were performed in different CA1 subregions of astrocyte-targeted transgenic mice. While confirming weak Ba 2ϩ sensitivity in situ, our data demonstrate that in freshly isolated astrocytes, the main proportion of membrane currents is sensitive to micromolar Ba 2ϩ concentrations. Upregulation of Kir4.1 transcripts and protein during the first 10 postnatal days was accompanied by a fourfold increase in astrocyte inward current density. Hippocampal astrocytes from Kir4.1Ϫ/Ϫ mice lacked Ba 2ϩ -sensitive currents. In addition, we report functional expression of K 2P channels of the TREK subfamily (TREK1, TREK2), which mediate astroglial outward currents. Together, our findings demonstrate that Kir4.1 constitutes the pivotal K ϩ channel subunit and that superposition of currents through Kir4.1 and TREK channels underlies the "passive" current pattern of hippocampal astrocytes.

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“…TASK-1 staining was included because there are controversial reports of TASK-1 expression in astrocytes, as measured by immunocytochemistry (Kindler et al, 2000;Rusznák et al, 2004).…”

Section: Immunocytochemical Staining For Twik-1 Trek-1 and Task-1 Imentioning

confidence: 99%

TWIK-1 and TREK-1 Are Potassium Channels Contributing Significantly to Astrocyte Passive Conductance in Rat Hippocampal Slices

Zhou¹,

Xu²,

Xie³

et al. 2009

Journal of Neuroscience

154

184

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Expression of a linear current-voltage (I-V) relationship (passive) Kϩ membrane conductance is a hallmark of mature hippocampal astrocytes. However, the molecular identifications of the K ϩ channels underlying this passive conductance remain unknown. We provide the following evidence supporting significant contribution of the two-pore domain K ϩ channel (K 2P ) isoforms, TWIK-1 and TREK-1, to this conductance. First, both passive astrocytes and the cloned rat TWIK-1 and TREK-1 channels expressed in CHO cells conduct significant amounts of Cs ϩ currents, but vary in their relative P Cs /P K permeability, 0.43, 0.10, and 0.05, respectively. Second, quinine, which potently inhibited TWIK-1 (IC 50 ϭ 85 M) and TREK-1 (IC 50 ϭ 41 M) currents, also inhibited astrocytic passive conductance by 58% at a concentration of 200 M. Third, a moderate sensitivity of passive conductance to low extracellular pH (6.0) supports a combined expression of acid-insensitive TREK-1, and to a lesser extent, acid-sensitive TWIK-1. Fourth, the astrocyte passive conductance showed low sensitivity to extracellular Ba 2ϩ , and extracellular Ba 2ϩ blocked TWIK-1 channels at an IC 50 of 960 M and had no effect on TREK-1 channels. Finally, an immunocytochemical study showed colocalization of TWIK-1 and TREK-1 proteins with the astrocytic markers GLAST and GFAP in rat hippocampal stratum radiatum. In contrast, another K 2P isoform TASK-1 was mainly colocalized with the neuronal marker NeuN in hippocampal pyramidal neurons and was expressed at a much lower level in astrocytes. These results support TWIK-1 and TREK-1 as being the major components of the long-sought K ϩ channels underlying the passive conductance of mature hippocampal astrocytes.

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Differential distribution of TASK-1, TASK-2 and TASK-3 immunoreactivities in the rat and human cerebellum

Cited by 34 publications

References 45 publications

Deafness associated changes in two-pore domain potassium channels in the rat inferior colliculus

Deafness associated changes in two-pore domain potassium channels in the rat inferior colliculus

Analysis of Astroglial K+ Channel Expression in the Developing Hippocampus Reveals a Predominant Role of the Kir4.1 Subunit

TWIK-1 and TREK-1 Are Potassium Channels Contributing Significantly to Astrocyte Passive Conductance in Rat Hippocampal Slices

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