Species-Specific Differences in Response to Anesthetics and Other Modulators by the K2P Channel TRESK

Keshavaprasad, Bharat; Liu, Canhui; Au, John; Kindler, Christoph; Cotten, Joseph F.; Yost, C. Spencer

doi:10.1213/01.ane.0000168447.87557.5a

Cited by 46 publications

(71 citation statements)

References 24 publications

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“…Later on, mouse (rodent) and human TRESK expression was found also in different regions of the central nervous system [20,25]. The pharmacology and biophysical properties of TRESK-mediated currents were studied mainly in heterologic expression systems.…”

Section: Discussionmentioning

confidence: 99%

TRESK-like potassium channels in leukemic T cells

Pottosin

Bonales-Alatorre

Valencia-Cruz

et al. 2008

Pflugers Arch - Eur J Physiol

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In this study, we present patch-clamp characterization of the background potassium current in human lymphoma (Jurkat cells), generated by voltage-independent 16 pS channels with a high ( approximately 100-fold) K+/Na+ selectivity. Depending on the background K+ channels density, from few per cell up to approximately 1 open channel per microm2, resting membrane potential was in the range of -40 to -83 mV, approaching E (K) = -88 mV. The background K+ channels were insensitive to margotoxin (3 nM), apamine (3 nM), and clotrimazole (1 microM), high-affinity blockers of the lymphocyte Kv1.3, SKCa2, and IKCa1 channels. The current depended weakly on external pH. Arachidonic acid (20 microM) and Hg2+ (0.3-10 microM) suppressed background K+ current in Jurkat cells by 75-90%. Background K+ current was weakly sensitive to TEA+ (IC50 = 14 mM), and was efficiently suppressed by externally applied bupivacaine (IC50 = 5 microM), quinine (IC50 = 16 microM), and Ba2+ (2 mM). Our data, in particular strong inhibition by mercuric ions, suggest that background K+ currents expressed in Jurkat cells are mediated by TWIK-related spinal cord K+ (TRESK) channels belonging to the double-pore domain K+ channel family. The presence of human TRESK in the membrane protein fraction was confirmed by Western blot analysis.

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Section: Discussionmentioning

confidence: 99%

TRESK-like potassium channels in leukemic T cells

Pottosin

Bonales-Alatorre

Valencia-Cruz

et al. 2008

Pflugers Arch - Eur J Physiol

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“…This could be the reason why mouse TRESK was originally named as TRESK-2 (152). As neither the human nor the mouse genome possesses more than one TRESK gene, it has been accepted that human and mouse TRESK channels are genuine orthologs (67,70,150,158).…”

Section: A Unique Single-channel Behaviormentioning

confidence: 99%

“…Mouse TRESK was shown to be expressed in the cerebrum, cerebellum, brain stem, spinal cord, and testis (70). TRESK mRNA was detected in the thymus and spleen of both mouse and rat (152) and in mouse DRG (81, 150,158).…”

Section: Physiological Significance Of Treskmentioning

confidence: 99%

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

Enyedi

Czirják

2010

Physiological Reviews

728

742

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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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“…Members of this potassium channel family attracted particular attention as the stimulation of their currents essentially contributed to the therapeutically important action of volatile anesthetics (7)(8)(9)(10). Among the 15 2PK ϩ channels, so far only TASK-1 and TASK-3 subunits have been shown to interact with 14-3-3␤ andthrough an unconventional (mode III) C-terminal motif.…”

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confidence: 99%

Phosphorylation-dependent Binding of 14-3-3 Proteins Controls TRESK Regulation

Czirják

Vuity

Enyedi

2008

Journal of Biological Chemistry

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The two-pore domain K ؉ channel, TRESK (TWIK-related spinal cord K ؉ channel) is reversibly activated by the calcium/ calmodulin-dependent protein phosphatase, calcineurin. In the present study, we report that 14-3-3 proteins directly bind to the intracellular loop of TRESK and control the kinetics of the calcium-dependent regulation of the channel. Coexpression of 14-3-3 with TRESK blocked, whereas the coexpression of a dominant negative form of 14-3-3 accelerated the return of the K ؉ current to the resting state after the activation mediated by calcineurin in Xenopus oocytes. The direct action of 14-3-3 was spatially restricted to TRESK, since 14-3-3 was also effective, when it was tethered to the channel by a flexible polyglutaminecontaining chain. The effect of both the coexpressed and chained 14-3-3 was alleviated by the microinjection of Ser(P)-Raf259 phosphopeptide that competes with TRESK for binding to 14-3-3. The ␥ and isoforms of 14-3-3 controlled TRESK regulation, whereas the ␤, , ⑀, , and isoforms failed to influence the mechanism significantly. Phosphorylation of serine 264 in mouse TRESK was required for the binding of 14-3-3. Because 14-3-3 proteins are ubiquitous, they are expected to control the duration of calcineurin-mediated TRESK activation in all the cell types that express the channel, depending on the phosphorylation state of serine 264. This kind of direct control of channel regulation by 14-3-3 is unique within the two-pore domain K ؉ channel family.Members of the 14-3-3 family are dimeric proteins, and each subunit possesses a single polypeptide binding groove (1). Proteins that bind these grooves typically encode either the RSXpSXP (mode I) or RX(Y/F)XpSXP (mode II) consensus motif (where X may be any amino acid, and pS denotes phosphoserine (2, 3). Several different interacting partners of 14-3-3 have been described, and 14-3-3 proved to be an important constituent of large protein complexes implicated in such diverse processes as the initiation of DNA replication, transcription, control of cell cycle, intracellular trafficking, and the modulation of ion channel function (4, 5).Two-pore domain potassium (2PK ϩ ) channels give rise to background (leak) K ϩ currents that are pivotal regulators of the excitability in neurons and other cell types (6). Members of this potassium channel family attracted particular attention as the stimulation of their currents essentially contributed to the therapeutically important action of volatile anesthetics (7-10). Among the 15 2PK ϩ channels, so far only TASK-1 and TASK-3 subunits have been shown to interact with 14-3-3␤ andthrough an unconventional (mode III) C-terminal motif. The binding of 14-3-3 overrides the endoplasmic reticulum retention signal and redirects these TASK channels to the cell surface (11-13).TRESK, 2 the 15th member of the 2PK ϩ channel family, was cloned from human spinal cord (14) and mouse cerebellum (15). Its mRNA is also expressed in the testis (15), spleen, thymus, placenta (16), and in the cerebrum (9). Recently, TRESK ...

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Species-Specific Differences in Response to Anesthetics and Other Modulators by the K2P Channel TRESK

Cited by 46 publications

References 24 publications

TRESK-like potassium channels in leukemic T cells

TRESK-like potassium channels in leukemic T cells

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

Phosphorylation-dependent Binding of 14-3-3 Proteins Controls TRESK Regulation

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Species-Specific Differences in Response to Anesthetics and Other Modulators by the K2P Channel TRESK

Cited by 46 publications

References 24 publications

TRESK-like potassium channels in leukemic T cells

TRESK-like potassium channels in leukemic T cells

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

Phosphorylation-dependent Binding of 14-3-3 Proteins Controls TRESK Regulation

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