Altered neuronal expression of TASK1 and TASK3 potassium channels in rodent and human autoimmune CNS inflammation

Meuth, Sven G.; Kanyshkova, Tatjana; Melzer, Nico; Bittner, Stefan; Kieseier, Bernd C.; Budde, Thomas; Wiendl, Heinz

doi:10.1016/j.neulet.2008.09.038

Cited by 14 publications

(10 citation statements)

References 24 publications

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“…Intense TASK-1-like immunoreactivity has been reported among white matter glial cells in the postnatal rat, although the cells were not previously identified (Kanjhan et al, 2004). TASK-1 mRNA has also previously been detected in the rat optic nerve, and was up-regulated in experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (Meuth et al, 2008). We also observed TASK-1 expression in astroglia, consistent with studies showing functional K 2P channels in astrocytes (Seifert et al, 2009; Zhou et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

TASK-1 channels in oligodendrocytes: A role in ischemia mediated disruption

Hawkins

Butt

2013

Neurobiology of Disease

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Oligodendrocytes are the myelinating cells of the CNS and, like neurons, are highly sensitive to ischemic damage. However, the mechanisms underlying cytotoxicity in oligodendrocytes during hypoxic/ischemic episodes are not fully understood. TASK-1 is a K+ leak channel that mediates hypoxic depolarisation in neurons. The expression and function of TASK-1 in oligodendrocytes had not previously been addressed. In this study, we investigate the expression of TASK-1 in oligodendrocytes and its role in white matter ischemic damage. Expression of TASK-1 in oligodendrocytes was investigated in the mouse brain using immunostaining. TASK-1 channel function was identified by established pharmacological and electrophysiological strategies, using the whole-cell patch clamp technique in cell cultures of oligodendrocytes from the optic nerve, a typical white matter tract. The role of TASK-1 in hypoxia was examined in isolated intact optic nerves subjected to oxygen glucose deprivation (OGD). Oligodendrocytes are strongly immunopositive for TASK-1 throughout the brain. Patch-clamp identified functional TASK-1-like leak currents in oligodendrocytes using two recognised means of inhibiting TASK-1, decreasing extracellular pH to 6.4 and exposure to the TASK-1 selective inhibitor anandamide. Incubation of optic nerves with methanandamide, a non-hydrolysable form of anandamide, significantly protected oligodendrocytes against hypoxic disruption and death in OGD. Our data demonstrate for the first time that oligodendrocytes express functional TASK-1 channels and provide compelling evidence they contribute to oligodendrocyte damage in hypoxia. Since oligodendrocyte damage is a key factor in ischemic episodes, TASK-1 may provide a potential therapeutic target in stroke and white matter disease.

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Section: Discussionmentioning

confidence: 99%

TASK-1 channels in oligodendrocytes: A role in ischemia mediated disruption

Hawkins

Butt

2013

Neurobiology of Disease

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“…Although many studies have speculated that potassium channels induce neuronal apoptosis [33, 34] or immune inflammatory injury [35], increasing evidence suggests that an important emerging therapeutic mechanism underlying neuroprotection is the activation/opening K 2P channels. Inflammatory plaques of human multiple sclerosis patients displayed profoundly lowered expression of TASK isoforms [15]. Rao et al found that traumatic brain injury led to a downregulation of potassium channels (RK5, TWIK, and X62859) in the injured cortex, leading to decreased posttraumatic axonal conductance and epilepsy [36].…”

Section: Discussionmentioning

confidence: 99%

“…Increased membrane excitability by TASK channel inhibition could contribute to increased electrical activity and subsequent neuronal degeneration caused by intracellular sodium and calcium accumulation, which is known as “excitotoxicity,” the most common pathological mechanism leading to neuronal death. Meuth et al [15] observed hypoxia depolarized central neurons after specific inhibition of TASK-1; they proposed that upregulation of functional TASK channel expression might exert a neuroprotective effect by dampening neuronal excitability. Neurons expressing nitric oxide (NO) synthase (NOS-I), which is upregulated in many human chronic neurodegenerative diseases, are highly susceptible to neurodegeneration.…”

Section: Discussionmentioning

confidence: 99%

“…Inhibition of the TASK-1 leads to an increased excitability of brainstem respiratory neurons, through further depolarization of cell membrane [11], thus enhancing the respiratory drive [13, 14]. Accompanied by its unique pharmacological profile, TASK-1 plays an extensive role in various physiological regulation activities including stress and inflammation and neuroimmune responses and is implicated in processes such as neuronal apoptosis [15]. …”

Section: Introductionmentioning

confidence: 99%

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The Effect of Mechanical Ventilation on TASK-1 Expression in the Brain in a Rat Model

Zhang

Wang

et al. 2017

Canadian Respiratory Journal

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Background and Objective TWIK-related acid-sensitive potassium channel 1 (TASK-1) is closely related to respiratory central control and neuronal injury. We investigated the effect of MV on TASK-1's functions and explored the mechanism using a rat model. Methods Male Sprague-Dawley rats were randomized to three groups: (1) high tidal volume (HVt): MV for four hours with Vt at 10 mL/kg; (2) low Vt (LVt): MV for four hours with Vt at 5 mL/kg; (3) basal (BAS): anesthetized and unventilated animals. We measured lung histology and plasma and brain levels of proteins (IL-6, TNF-α, and S-100B) and determined TASK-1 levels in rat brainstems as a marker of respiratory centre activity. Results The LISs (lung injury scores) were significantly higher in the HVt group. Brain inflammatory cytokines levels were different to those in serum. TASK-1 levels were significantly lower in the MV groups (P = 0.002) and the HVt group tended to have a lower level of TASK-1 than the LVt group. Conclusion MV causes not only lung injury, but also brain injury. MV affects the regulation of the respiratory centre, perhaps causing damage to it. Inflammation is probably not the main mechanism of ventilator-related brain injury.

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“…This cation influx is counterbalanced by several potassium outward currents in order to stabilize the membrane potential and preserve the driving force. Among them are the voltage-gated K + channel K V 1.3 (KCNA3; (Rangaraju et al, 2009;Wulff et al, 2003)), the Ca 2+ -dependent K + channel K Ca 3.1 (KCNN4; (Lam and Wulff, 2011;Orban et al, 2014;Panyi et al, 2006)), the TWIK-related acid-sensing K + channel 1-3 (TASK1-3, Kcnk3,5,9;(Bittner et al, 2010;Bittner et al, 2012;Bittner et al, 2009;Bittner et al, 2011;Meuth et al, 2008a;Meuth et al, 2008b;Meuth et al, 2009) and the TWIK-related spinal cord K + channel (TRESK, Kcnk18;(Han and Kang, 2009;Pottosin et al, 2008)). …”

Section: Immune Cells Express Various Ion Channels With Very Diverse mentioning

confidence: 99%

Human T cells in silico: Modelling their electrophysiological behaviour in health and disease

Ehling

Meuth

Eichinger

et al. 2016

Journal of Theoretical Biology

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Altered neuronal expression of TASK1 and TASK3 potassium channels in rodent and human autoimmune CNS inflammation

Cited by 14 publications

References 24 publications

TASK-1 channels in oligodendrocytes: A role in ischemia mediated disruption

TASK-1 channels in oligodendrocytes: A role in ischemia mediated disruption

The Effect of Mechanical Ventilation on TASK-1 Expression in the Brain in a Rat Model

Human T cells in silico: Modelling their electrophysiological behaviour in health and disease

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