Recombinant hTASK1 Is an O2-Sensitive K+ Channel

Lewis, Anthony; Hartness, Matthew E.; Chapman, C.G.; Fearon, Ian M.; Meadows, Helen; Peers, Chris; Kemp, Paul J.

doi:10.1006/bbrc.2001.5310

Cited by 70 publications

(35 citation statements)

References 19 publications

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“…In contrast to acidosis, hypoxia-induced inhibition of TASK channels depends on cellular integrity (38) and the cell type in which the channel is expressed [e.g., it is absent in Xenopus oocytes (267), but operates in HEK cells (156,196)]. Several indirect mechanisms have been proposed by which hypoxia influences the activity of oxygen-sensitive potassium channels.…”

Section: Chemoreception In the Carotid Bodymentioning

confidence: 99%

Molecular Background of Leak K⁺Currents: Two-Pore Domain Potassium Channels

Enyedi

Czirják

2010

Physiological Reviews

777

769

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Two-pore domain K+ (K2P) channels give rise to leak (also called background) K+ currents. The well-known role of background K+ currents is to stabilize the negative resting membrane potential and counterbalance depolarization. However, it has become apparent in the past decade (during the detailed examination of the cloned and corresponding native K2P channel types) that this primary hyperpolarizing action is not performed passively. The K2P channels are regulated by a wide variety of voltage-independent factors. Basic physicochemical parameters (e.g., pH, temperature, membrane stretch) and also several intracellular signaling pathways substantially and specifically modulate the different members of the six K2P channel subfamilies (TWIK, TREK, TASK, TALK, THIK, and TRESK). The deep implication in diverse physiological processes, the circumscribed expression pattern of the different channels, and the interesting pharmacological profile brought the K2P channel family into the spotlight. In this review, we focus on the physiological roles of K2P channels in the most extensively investigated cell types, with special emphasis on the molecular mechanisms of channel regulation.

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Section: Chemoreception In the Carotid Bodymentioning

confidence: 99%

Molecular Background of Leak K⁺Currents: Two-Pore Domain Potassium Channels

Enyedi

Czirják

2010

Physiological Reviews

777

769

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“…However, it is becoming more evident that these channels have diverse mechanisms of modulation. Factors influencing these channels include extracellular pH (Duprat et al 1997), membrane stretch, arachidonic acid (Bang et al 2000, Miller et al 2003 and oxygen tension (hypoxia; Lewis et al 2001, Miller et al 2003.…”

Section: Introductionmentioning

confidence: 99%

Expression of TASK and TREK, two-pore domain K+ channels, in human myometrium

Bai¹,

Bugg²,

Greenwood³

et al. 2005

Reproduction

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Two-pore domain K 1 channels are an emerging family of K 1 channels that may contribute to setting membrane potential in both electrically excitable and non-excitable cells and, as such, influence cellular function. The human uteroplacental unit contains both excitable (e.g. myometrial) and non-excitable cells, whose function depends upon the activity of K 1 channels.We have therefore investigated the expression of two members of this family, TWIK (two-pore domain weak inward rectifying K 1 channel)-related acid-sensitive K 1 channel (TASK) and TWIK-related K 1 channel (TREK) in human myometrium. Using RT-PCR the mRNA expression of TASK and TREK isoforms was examined in myometrial tissue from pregnant women. mRNAs encoding TASK1, 4 and 5 and TREK1 were detected whereas weak or no signals were observed for TASK2, TASK3 and TREK2. Western blotting for TASK1 gave two bands of approximately 44 and 65 kDa, whereas TREK1 gave bands of approximately 59 and 90 kDa in myometrium from pregnant women. TASK1 and TREK1 immunofluorescence was prominent in intracellular and plasmalemmal locations within myometrial cells. Therefore, we conclude that the human myometrium is a site of expression for the two-pore domain K 1 channel proteins TASK1 and TREK1.Reproduction (

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“…10 Hypoxia is known to modulate the activity of a wide range of ion channels in central neurons and other tissues (reviewed by Lopez-Barneo et al 12 ), and native TASKs of both carotid body glomus cells 13 and a human cell line 14 and recombinant TASK-1 have recently been shown to be inhibited by acute hypoxia. 15 Since experimentally induced hypoxia in nervous tissue not only causes depolarization but can also result in acidosis and neurotransmitter release, and since similar effects are seen in clinical conditions that result in hypoxia, such as stroke, 1,2 we hypothesized that the underlying mechanism for this response is hypoxic inhibition of TASK-1. The aim of this study, therefore, was to determine the functional consequences of hypoxia in a neuron known to express TASK-1 and to determine whether this response is a result of hypoxic inhibition of native TASK-1 channels.…”

mentioning

confidence: 99%

Hypoxic Depolarization of Cerebellar Granule Neurons by Specific Inhibition of TASK-1

Plant

Kemp

Peers

et al. 2002

Stroke

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Background and Purpose-The mechanisms underlying neuronal excitotoxicity during hypoxic/ischemic episodes are not fully understood. One feature of such insults is a rapid and transient depolarization of central neurons. TASK-1, an open rectifying K ϩ leak channel, is significant in setting the resting membrane potential of rat cerebellar granule neurons by mediating a standing outward K ϩ current. In this study we investigate the theory that the transient neuronal depolarization seen during hypoxia is due to the inhibition of TASK-1. Methods-Activity of TASK-1 in primary cultures of rat cerebellar granule neurons was investigated by the whole-cell patch-clamp technique. Discriminating pharmacological and electrophysiological maneuvers were used to isolate the specific channel types underlying acute hypoxic depolarizations. Results-Exposure of cells to acute hypoxia resulted in a reversible and highly reproducible mean membrane depolarization of 14.2Ϯ2.6 mV (nϭ5; PϽ0.01). Two recognized means of inhibiting TASK-1 (decreasing extracellular pH to 6.4 or exposure to the TASK-1-selective inhibitor anandamide) abolished both the hypoxic depolarization and the hypoxic depression of a standing outward current, identifying TASK-1 as the channel mediating this effect. Conclusions-Our data provide compelling evidence that hypoxia depolarizes central neurons by specific inhibition of TASK-1. Since this hypoxic depolarization may be an early, contributory factor in the response of central neurons to hypoxic/ischemic episodes, TASK-1 may provide a potential therapeutic target in the treatment of stroke.

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Recombinant hTASK1 Is an O2-Sensitive K+ Channel

Cited by 70 publications

References 19 publications

Molecular Background of Leak K⁺Currents: Two-Pore Domain Potassium Channels

Molecular Background of Leak K⁺Currents: Two-Pore Domain Potassium Channels

Expression of TASK and TREK, two-pore domain K+ channels, in human myometrium

Hypoxic Depolarization of Cerebellar Granule Neurons by Specific Inhibition of TASK-1

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Recombinant hTASK1 Is an O2-Sensitive K+ Channel

Cited by 70 publications

References 19 publications

Molecular Background of Leak K+Currents: Two-Pore Domain Potassium Channels

Molecular Background of Leak K+Currents: Two-Pore Domain Potassium Channels

Expression of TASK and TREK, two-pore domain K+ channels, in human myometrium

Hypoxic Depolarization of Cerebellar Granule Neurons by Specific Inhibition of TASK-1

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Molecular Background of Leak K⁺Currents: Two-Pore Domain Potassium Channels

Molecular Background of Leak K⁺Currents: Two-Pore Domain Potassium Channels