Expression Pattern in Brain of TASK-1, TASK-3, and a Tandem Pore Domain K+ Channel Subunit, TASK-5, Associated with the Central Auditory Nervous System

Karschin, Christine; Wischmeyer, Erhard; Preisig‐Müller, Regina; Rajan, Sindhu; Derst, Christian; Grzeschik, Karl‐Heinz; Daut, Jürgen; Karschin, Andreas

doi:10.1006/mcne.2001.1045

Cited by 126 publications

(145 citation statements)

References 45 publications

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“…tent with the report that in MS/DB nuclei many neurons expressed moderate to abundant amount of TASK1 mRNA whereas there were only few neurons that abundantly express TASK3 mRNA (Karschin et al, 2001). Furthermore, the dynamic modulations of TASK1-like pH sensitivity of the I-K leak by PKG activation and inhibition (Fig.…”

Section: Modulation Of Task1-mediated I-k Leak In Cholinergic Bf Neuronssupporting

confidence: 88%

Protein Kinase G Dynamically Modulates TASK1-Mediated Leak K⁺Currents in Cholinergic Neurons of the Basal Forebrain

Toyoda¹,

Saito²,

Okazawa³

et al. 2010

J. Neurosci.

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Leak Kϩ conductance generated by TASK1/3 channels is crucial for neuronal excitability. However, endogenous modulators activating TASK channels in neurons remained unknown. We previously reported that in the presumed cholinergic neurons of the basal forebrain (BF), activation of NO-cGMP-PKG (protein kinase G) pathway enhanced the TASK1-like leak K ϩ current (I-K leak ). As 8-Br-cGMP enhanced the I-K leak mainly at pH 7.3 as if changing the I-K leak from TASK1-like to TASK3-like current, such an enhancement of the I-K leak would result either from an enhancement of hidden TASK3 component or from an acidic shift in the pH sensitivity profile of TASK1 component. In view of the report that protonation of TASK channel decreases its open probability, the present study was designed to examine whether the activation of PKG increases the conductance of TASK1 channels by reducing their binding affinity for H ϩ , i.e., by increasing K d for protonation, or not. We here demonstrate that PKG activation and inhibition respectively upregulate and downregulate TASK1 channels heterologously expressed in PKG-loaded HEK293 cells at physiological pH, by causing shifts in the K d in the acidic and basic directions, respectively. Such PKG modulations of TASK1 channels were largely abolished by mutating pH sensor H98. In the BF neurons that were identified to express ChAT and TASK1 channels, similar dynamic modulations of TASK1-like pH sensitivity of I-K leak were caused by PKG. It is strongly suggested that PKG activation and inhibition dynamically modulate TASK1 currents at physiological pH by bidirectionally changing K d values for protonation of the extracellular pH sensors of TASK1 channels in cholinergic BF neurons.

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Section: Modulation Of Task1-mediated I-k Leak In Cholinergic Bf Neuronssupporting

confidence: 88%

Protein Kinase G Dynamically Modulates TASK1-Mediated Leak K⁺Currents in Cholinergic Neurons of the Basal Forebrain

Toyoda¹,

Saito²,

Okazawa³

et al. 2010

J. Neurosci.

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“…In striatum, TREK-1 (K 2P 2.1, Kcnk2) is evenly distributed in a pattern most consistent with expression in medium spiny neurons (Heurteaux et al 2004;Talley et al 2001). On the other hand, TASK-3 is expressed in relatively large cells in a diffuse pattern similar to that of cholinergic interneurons (Karschin et al 2001;Talley et al 2001). In this study, we used histochemical and electrophysiological approaches to show that TASK-3 channels are functionally expressed in these cells, where they provide a background K ϩ conductance that contributes to the membrane potential; these predominantly homomeric, native TASK-3-like currents proved resistant to modulation by G␣q-coupled receptors, suggesting that some aspect of the signaling mechanism linking receptors to TASK channels is disrupted in striatal cholinergic interneurons.…”

Section: Introductionmentioning

confidence: 84%

Striatal Cholinergic Interneurons Express a Receptor-Insensitive Homomeric TASK-3–Like Background K⁺ Current

Berg

Bayliss²

2007

Journal of Neurophysiology

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Berg AP, Bayliss DA. Striatal cholinergic interneurons express a receptor-insensitive homomeric TASK-3-like background K ϩ current. J Neurophysiol 97: 1546 -1552, 2007. First published December 13, 2006; doi:10.1152/jn.01090.2006. Large aspiny cholinergic interneurons provide the sole source of striatal acetylcholine, a neurotransmitter essential for normal basal ganglia function. Cholinergic interneurons engage in multiple firing patterns that depend on interactions among various voltagedependent ion channels active at different membrane potentials. Leak conductances, particularly leak K ϩ channels, are of primary importance in establishing the prevailing membrane potential. We have combined molecular neuroanatomy with whole cell electrophysiology to demonstrate that TASK-3 (K 2P 9.1, Kcnk9) subunits contribute to leak K ϩ currents in striatal cholinergic interneurons. Immunostaining for choline acetyltransferase was combined with TASK-3 labeling, using nonradioactive cRNA probes or antisera selective for TASK-3, to demonstrate that striatal cholinergic neurons universally express TASK-3. Consistent with this, we isolated a pH-, anesthetic-, and Zn 2ϩ -sensitive current with properties expected of TASK-3 homodimeric channels. Surprisingly, activation of G␣q-linked receptors (metabotropic glutamate mGluR1/5 or histamine H1) did not appear to modulate native interneuron TASK-3-like currents. Together, our data indicate that homomeric TASK-3-like background K ϩ currents contribute to establishing membrane potential in striatal cholinergic interneurons and they suggest that receptor modulation of TASK channels is dependent on cell context. I N T R O D U C T I O NAcetylcholine (ACh) is essential for striatal function and changes in striatal cholinergic drive are implicated in the pathophysiology of movement disorders (Calabresi et al. 2000). A sparse population of large aspiny cholinergic interneurons provides the sole source of striatal ACh and regulation of membrane excitability of interneurons is therefore integral to many aspects of striatal function.Cholinergic interneurons discharge spontaneously in either a tonic or bursting pattern. The expression of these distinct firing patterns involves complex interactions among various voltagedependent ion channels-TTX-sensitive sodium channels; hyperpolarization-activated HCN channels; voltage-sensitive, inwardly rectifying, and calcium-activated K . In striatum, TREK-1 (K 2P 2.1, Kcnk2) is evenly distributed in a pattern most consistent with expression in medium spiny neurons (Heurteaux et al. 2004;Talley et al. 2001). On the other hand, TASK-3 is expressed in relatively large cells in a diffuse pattern similar to that of cholinergic interneurons (Karschin et al. 2001;Talley et al. 2001). In this study, we used histochemical and electrophysiological approaches to show that TASK-3 channels are functionally expressed in these cells, where they provide a background K ϩ conductance that contributes to the membrane potential; these predominantly homomeric, native TASK-3-...

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“…Expression of TASK channel transcripts is widespread throughout the CNS (Karschin et al, 2001;Talley et al, 2001;Vega-Saenz et al, 2001), and it is now clear that TASK-like background K ϩ currents contribute to regulation of excitability in numerous cell types (Millar et al, 2000;Sirois et al, 2000;Han et al, 2003;Meuth et al, 2003Meuth et al, , 2006Berg et al, 2004;Aller et al, 2005;Taverna et al, 2005;Burdakov et al, 2006;Torborg et al, 2006;Brickley et al, 2007), including many central respiratory-related neurons Washburn et al, 2002Washburn et al, , 2003. In addition, it has been proposed that TASK channels may be involved in regulation of respiration by peripheral chemoreceptors (e.g., via hypoxic inhibition of TASK-like channels in carotid body glomus cells) (Buckler, 2007).…”

Section: Task Channel Contributions To Respirationmentioning

confidence: 99%

TASK Channels Determine pH Sensitivity in Select Respiratory Neurons But Do Not Contribute to Central Respiratory Chemosensitivity

Mulkey¹,

Talley²,

Stornetta³

et al. 2007

J. Neurosci.

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Central respiratory chemoreception is the mechanism by which the CNS maintains physiologically appropriate pH and PCO 2 via control of breathing. A prominent hypothesis holds that neural substrates for this process are distributed widely in the respiratory network, especially because many neurons that make up this network are chemosensitive in vitro. We and others have proposed that TASK channels (TASK-1, K 2P 3.1 and/or TASK-3, K 2P 9.1) may serve as molecular sensors for central chemoreception because they are highly expressed in multiple neuronal populations in the respiratory pathway and contribute to their pH sensitivity in vitro. To test this hypothesis, we examined the chemosensitivity of two prime candidate chemoreceptor neurons in vitro and tested ventilatory responses to CO 2 using TASK channel knock-out mice. The pH sensitivity of serotonergic raphe neurons was abolished in TASK channel knock-outs. In contrast, pH sensitivity of neurons in the mouse retrotrapezoid nucleus (RTN) was fully maintained in a TASK null background, and pharmacological evidence indicated that a K ϩ channel with properties distinct from TASK channels contributes to the pH sensitivity of rat RTN neurons. Furthermore, the ventilatory response to CO 2 was completely retained in single or double TASK knock-out mice. These data rule out a strict requirement for TASK channels or raphe neurons in central respiratory chemosensation. Furthermore, they indicate that a non-TASK K ϩ current contributes to chemosensitivity of RTN neurons, which are profoundly pH-sensitive and capable of driving respiratory output in response to local pH changes in vivo.

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Expression Pattern in Brain of TASK-1, TASK-3, and a Tandem Pore Domain K+ Channel Subunit, TASK-5, Associated with the Central Auditory Nervous System

Cited by 126 publications

References 45 publications

Protein Kinase G Dynamically Modulates TASK1-Mediated Leak K⁺Currents in Cholinergic Neurons of the Basal Forebrain

Protein Kinase G Dynamically Modulates TASK1-Mediated Leak K⁺Currents in Cholinergic Neurons of the Basal Forebrain

Striatal Cholinergic Interneurons Express a Receptor-Insensitive Homomeric TASK-3–Like Background K⁺ Current

TASK Channels Determine pH Sensitivity in Select Respiratory Neurons But Do Not Contribute to Central Respiratory Chemosensitivity

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Expression Pattern in Brain of TASK-1, TASK-3, and a Tandem Pore Domain K+ Channel Subunit, TASK-5, Associated with the Central Auditory Nervous System

Cited by 126 publications

References 45 publications

Protein Kinase G Dynamically Modulates TASK1-Mediated Leak K+Currents in Cholinergic Neurons of the Basal Forebrain

Protein Kinase G Dynamically Modulates TASK1-Mediated Leak K+Currents in Cholinergic Neurons of the Basal Forebrain

Striatal Cholinergic Interneurons Express a Receptor-Insensitive Homomeric TASK-3–Like Background K+ Current

TASK Channels Determine pH Sensitivity in Select Respiratory Neurons But Do Not Contribute to Central Respiratory Chemosensitivity

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Protein Kinase G Dynamically Modulates TASK1-Mediated Leak K⁺Currents in Cholinergic Neurons of the Basal Forebrain

Protein Kinase G Dynamically Modulates TASK1-Mediated Leak K⁺Currents in Cholinergic Neurons of the Basal Forebrain

Striatal Cholinergic Interneurons Express a Receptor-Insensitive Homomeric TASK-3–Like Background K⁺ Current