TRESK-like potassium channels in leukemic T cells

Pottosin, Igor; Bonales-Alatorre, Edgar; Valencia-Cruz, Georgina; Mendoza-Magaña, María Luisa; Dobrovinskaya, Oxana

doi:10.1007/s00424-008-0481-x

Cited by 34 publications

(34 citation statements)

References 41 publications

(93 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nevertheless, the functional expression of K2P (KCNK) channels in the immune cells has been rarely investigated. Except our own reports, only two studies have detected the expression of K2P channels (TASK and TRESK) in T lymphocytes (21,26).…”

Section: Discussionmentioning

confidence: 68%

Identification of the large-conductance background K⁺ channel in mouse B cells as TREK-2

Zheng¹,

Nam²,

Pang³

et al. 2009

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

Mouse B cells and their cell line (WEHI-231) express large-conductance background K(+) channels (LK(bg)) that are activated by arachidonic acids, characteristics similar to TREK-2. However, there is no evidence to identify the molecular nature of LK(bg); some properties of LK(bg) were partly different from the reported results of TREK type channels. In this study, we compared the properties of cloned TREK-2 and LK(bg) in terms of their sensitivities to ATP, phosphatidylinositol 4,5-bisphosphate (PIP(2)), intracellular pH (pH(i)), and membrane stretch. Similar to the previous findings of LK(bg), TREK-2 showed spontaneous activation after membrane excision (i-o patch) and were inhibited by MgATP or by PIP(2). The inhibition by MgATP was prevented by wortmannin, suggesting membrane-delimited regulation of TREKs by phosphoinositide (PI) kinase. The same was observed with the property of LK(bg); the activation of TREK-2 by membrane stretch was suppressed by U73122 (PLC inhibitor). As with the known properties of TREK-2, LK(bg) were activated by acidic pH(i) and inhibited by PKC activator. Finally, we confirmed the expression of TREK-2 in WEHI-231 by using RT-PCR and immunoblot analyses. The amplitude of background K(+) current and the TREK-2 expression in WEHI-231 were commonly decreased by genetic knockdown of TREK-2 using small interfering RNA. The downregulation of TREK-2 attenuated Ca(2+)-influx induced by arachidonic acid in WEHI-231. As a whole, these results strongly indicate that TREK-2 encodes LK(bg) in mouse B cells. We also newly suggest that the low activity of TREK-2 in intact cells is due to the inhibition by intrinsic PIP(2).

show abstract

Section: Discussionmentioning

confidence: 68%

Identification of the large-conductance background K⁺ channel in mouse B cells as TREK-2

Zheng¹,

Nam²,

Pang³

et al. 2009

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

show abstract

“…Abundant expression of TRESK in the sensory neurons of dorsal root and trigeminal ganglia (1,2,7), and the high sensitivity to anesthetics (30 -35) and the paresthesia-inducing hydroxy-␣-sanshool (8) led to the hypothesis that the channel is important in the somatosensory function with special respect to pain sensation (9 -11). On the other hand, TRESK expression was reported in rat thymus and spleen (6), and recently in Jurkat human leukemic T lymphocytes (36,37). This localization and the unique regulation of the channel by calcineurin (a major target of extensively used immunosuppressant drugs) led to the suggestion that TRESK could be involved in T-cell-mediated immune functions (38).…”

Section: Discussionmentioning

confidence: 99%

TRESK Background K+ Channel Is Inhibited by Phosphorylation via Two Distinct Pathways

Czirják¹,

Enyedi

2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

The two-pore domain K ؉ channel, TRESK (TWIK-related spinal cord K ؉ channel, KCNK18) is directly regulated by the calcium/calmodulin-dependent phosphatase calcineurin and 14-3-3 adaptor proteins. The calcium signal robustly activates the channel via calcineurin, whereas the anchoring of 14-3-3 interferes with the return of the current to the resting state after the activation in Xenopus oocytes. In the present study, we report that the phosphorylation of TRESK at two distinct regulatory regions, the 14-3-3 binding site (Ser-264) and the cluster of three adjacent serine residues (Ser-274, Ser-276, and Ser-279), are responsible for channel inhibition. The phosphorylation of Ser-264 by protein kinase A accelerated the return of the current of S276E mutant TRESK to the resting state after the calcineurin-dependent activation. In the presence of 14-3-3, the basal current of the S276E mutant was reduced, and its calcineurin-dependent activation was augmented, suggesting that the direct binding of the adaptor protein to TRESK contributed to the basal inhibition of the channel under resting conditions. Unexpectedly, we found that 14-3-3 impeded the recovery of the current of S264E mutant TRESK to the resting state after the calcineurin-dependent activation, despite of the mutated 14-3-3 binding site. This suggests that 14-3-3 inhibited the kinase phosphorylating the regulatory cluster of Ser-274, Ser-276, and Ser-279, independently of the direct interaction between TRESK and 14-3-3. In conclusion, two distinct inhibitory kinase pathways converge on TRESK, and their effect on the calcineurin-dependent regulation is differentially modulated by the functional availability of 14-3-3.The two-pore domain K ϩ channel, TRESK 3 (TWIK-related spinal cord K ϩ channel, KCNK18) is a major background K ϩ channel of pseudounipolar sensory neurons (1-3). Abundant expression of TRESK mRNA and protein has been detected in dorsal root ganglia (DRG) (1, 2). TRESK cDNA was originally cloned from human spinal cord (4), and subsequently from mouse cerebellum (5) and testis (6). The distribution of the immunolocalization of TRESK in different central nervous system regions has also been recently reported (7). In DRG neurons, TRESK current was reliably identified at the single channel level (1). It was found to be the most prominent determinant of the resting K ϩ conductance of the plasma membrane together with another two-pore domain K ϩ (K2P) channel, TREK-2 (1, 2). TRESK has recently attracted particular attention, because of its efficient inhibition by the paresthesia-inducing pungent agents of the medicinal herb Szechuan pepper (8) and because of its probable role in nociception (9 -11).Although TRESK is abundant in DRG neurons, its coexpression with other two-pore domain K ϩ (K2P) channels (against which no selective inhibitors exist at present) impedes its examination as a whole cell current. Therefore we embarked on the investigation of this important K ϩ channel in a heterologous system, in Xenopus laevis oocytes. We demonstrated that...

show abstract

“…In human and murine T lymphocytes, three distinct members of the two-pore potassium channel family are constitutively expressed: TASK1, TASK2 and TASK3. In addition, the expression of the calcineurin-regulated K 2P channel TRESK was postulated in leukemic Jurkat T cells [16]. The functional role of TRESK in primary T cells still needs to be confirmed.…”

Section: K + Channelsmentioning

confidence: 99%

Ion channels in autoimmune neurodegeneration

et al. 2011

View full text Add to dashboard Cite

a b s t r a c tMultiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by widespread inflammation, focal demyelination and a variable degree of axonal and neuronal loss. Ionic conductances regulate T cell activation as well as neuronal function and thus have been found to play a crucial role in MS pathogenesis. Since present therapeutical approaches are only partially effective so far, ion channel modulation as a future strategy was brought into focus. Here, we review the status quo concerning recent findings from ion channel research in MS and its animal model, experimental autoimmune encephalomyelitis.

show abstract

TRESK-like potassium channels in leukemic T cells

Cited by 34 publications

References 41 publications

Identification of the large-conductance background K⁺ channel in mouse B cells as TREK-2

Identification of the large-conductance background K⁺ channel in mouse B cells as TREK-2

TRESK Background K+ Channel Is Inhibited by Phosphorylation via Two Distinct Pathways

Ion channels in autoimmune neurodegeneration

Contact Info

Product

Resources

About

TRESK-like potassium channels in leukemic T cells

Cited by 34 publications

References 41 publications

Identification of the large-conductance background K+ channel in mouse B cells as TREK-2

Identification of the large-conductance background K+ channel in mouse B cells as TREK-2

TRESK Background K+ Channel Is Inhibited by Phosphorylation via Two Distinct Pathways

Ion channels in autoimmune neurodegeneration

Contact Info

Product

Resources

About

Identification of the large-conductance background K⁺ channel in mouse B cells as TREK-2

Identification of the large-conductance background K⁺ channel in mouse B cells as TREK-2