K<sub>bg</sub>and Kv1.3 channels mediate potassium efflux in the early phase of apoptosis in Jurkat T lymphocytes

Valencia-Cruz, Georgina; Shabala, Lana; Delgado‐Enciso, Iván; Shabala, Sergey; Bonales-Alatorre, Edgar; Pottosin, Igor; Dobrovinskaya, Oxana

doi:10.1152/ajpcell.00064.2009

Cited by 41 publications

(42 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Adequate inhibition of potassium channels is thought to cause membrane depolarization and activate voltage-dependent calcium channels, leading to cell proliferation (Burg et al, 2008). Additionally, activation of potassium channels plays an important role at an early stage of apoptosis (Burg et al, 2008;Valencia-Cruz et al, 2009). In the present study, noradrenaline increased DNA synthesis at a low dose and decreased it at a high dose ( Figure 4A).…”

Section: Discussionsupporting

confidence: 53%

Noradrenaline stimulates cell proliferation by suppressing potassium channels via G_i/o‐protein‐coupled α_1B‐adrenoceptors in human osteoblasts

Kodama

Togari

2013

British J Pharmacology

View full text Add to dashboard Cite

BACKGROUND AND PURPOSERecent studies demonstrated that the sympathetic nervous system regulates bone metabolism via b2-adrenoceptors. Although a-adrenoceptors are also expressed in osteogenic cells, their functions in bone metabolism have been less studied. We previously demonstrated that noradrenaline suppressed potassium currents via a1B-adrenoceptors in the human osteoblast SaM-1 cell line. The aim of this study was to investigate the signal transduction pathway and the physiological role of noradrenaline in human osteoblasts in more detail. EXPERIMENTAL APPROACHTo investigate signal transduction through a1B-adrenoceptors, we used whole-cell patch clamp recording and Ca fluorescence imaging. Potassium channels regulate membrane potential and cell proliferation activity in non-excitable cells, so we evaluated cell proliferation activity by BrdU incorporation and WST assay. KEY RESULTSIn SaM-1 cells, bath-applied noradrenaline elevated intracellular Ca 2+ concentration and this effect was abolished by both chloroethylclonidine, an a1B-adrenoceptor antagonist, and U73122, a PLC inhibitor. However, the inhibitory effect of noradrenaline on whole-cell current was unaffected by U73122. In contrast, in cells pretreated with either Pertussis toxin, a Gi/o-protein-coupled receptor inhibitor, or gallein, a Gbg-protein inhibitor, the inhibitory effect of noradrenaline on whole-cell current was significantly suppressed. Noradrenaline-induced enhancement of cell proliferation was inhibited by CsCl, a non-selective potassium channel blocker, gallein and H89, a PKA inhibitor, but not by U73122. CONCLUSIONS AND IMPLICATIONSNoradrenaline facilitated cell proliferation by regulation of potassium currents in human osteoblasts via Gi/o-protein-coupled a1B-adrenoceptors, not via coupling to Gq-proteins. Abbreviationsa-MEM, a-modified minimum essential medium; BK channel, large-conductance calcium-activated potassium channel; BrdU, 5-bromo-2′

show abstract

Section: Discussionsupporting

confidence: 53%

Noradrenaline stimulates cell proliferation by suppressing potassium channels via G_i/o‐protein‐coupled α_1B‐adrenoceptors in human osteoblasts

Kodama

Togari

2013

British J Pharmacology

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 two recent reports, an instantaneous, noninactivating outward K ϩ current of human leukemic (Jurkat) T cells was attributed to TRESK (278,322). The pharmacological properties of this current were comparable to those of TRESK, and the single-channel conductance was also in the appropriate range.…”

Section: Physiological Significance Of Treskmentioning

confidence: 95%

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

Enyedi

Czirják

2010

Physiological Reviews

734

760

View full text Add to dashboard Cite

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.

show abstract

K_bgand Kv1.3 channels mediate potassium efflux in the early phase of apoptosis in Jurkat T lymphocytes

Cited by 41 publications

References 55 publications

Noradrenaline stimulates cell proliferation by suppressing potassium channels via G_i/o‐protein‐coupled α_1B‐adrenoceptors in human osteoblasts

Noradrenaline stimulates cell proliferation by suppressing potassium channels via G_i/o‐protein‐coupled α_1B‐adrenoceptors in human osteoblasts

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

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

Contact Info

Product

Resources

About

Kbgand Kv1.3 channels mediate potassium efflux in the early phase of apoptosis in Jurkat T lymphocytes

Cited by 41 publications

References 55 publications

Noradrenaline stimulates cell proliferation by suppressing potassium channels via Gi/o‐protein‐coupled α1B‐adrenoceptors in human osteoblasts

Noradrenaline stimulates cell proliferation by suppressing potassium channels via Gi/o‐protein‐coupled α1B‐adrenoceptors in human osteoblasts

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

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

Contact Info

Product

Resources

About

K_bgand Kv1.3 channels mediate potassium efflux in the early phase of apoptosis in Jurkat T lymphocytes

Noradrenaline stimulates cell proliferation by suppressing potassium channels via G_i/o‐protein‐coupled α_1B‐adrenoceptors in human osteoblasts

Noradrenaline stimulates cell proliferation by suppressing potassium channels via G_i/o‐protein‐coupled α_1B‐adrenoceptors in human osteoblasts

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