TASK, TREK &amp; Co.: a mutable potassium channel family for diverse tasks in the brain

In multiple sclerosis, demyelination occurs as a consequence of chronic autoimmunity in the central nervous system causing progressive neurological impairment in patients. After a demyelinating event, new myelin sheaths are formed by adult oligodendroglial progenitor cells; a process called remyelination. However, remyelination often fails in multiple sclerosis due to insufficient recruitment and differentiation of oligodendroglial precursor cells. A pivotal role for the twopore-domain potassium (K 2P ) channel, TASK1, has already been proven for an animal model of multiple sclerosis. However, the mechanisms underlying the TASK1-mediated effects are still elusive. Here, we tested the role of TASK1 channels in oligodendroglial differentiation and remyelination after cuprizone-induced demyelination in male mice. We found TASK1 channels to be functionally expressed on primary murine and human, pluripotent stem cell-derived oligodendrocytes. Lack of TASK1 channels resulted in an increase of mature oligodendrocytes in vitro as well as a higher number of mature oligodendrocytes and accelerated developmental myelination in vivo. Mechanistically, Task1-deficient cells revealed a higher amount of phosphorylated WNK1, a kinase known to be involved in the downstream signaling of the myelination regulator LINGO-1. Furthermore, we analyzed the effect of genetic TASK1 ablation or pharmacological TASK1 inhibition on disease-related remyelination. Neither channel inhibition nor lack of TASK1 channels promoted remyelination after pathological demyelination. In summary, we conclude that functional TASK1 channels participate in the modulation of differentiating oligodendroglial cells in a previously unknown manner. However, while being involved in developmental myelination our data suggest that TASK1 channels have no major effect on remyelination. K E Y W O R D S multiple sclerosis, myelination, oligodendrocyte, remyelination, TASK1 channel

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The K_2P‐channel TASK1 affects Oligodendroglial differentiation but not myelin restoration

Albrecht

Korr

Nowack

et al. 2019

Glia

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TASK, TREK & Co.: a mutable potassium channel family for diverse tasks in the brain

Cited by 1 publication

References 58 publications

The K_2P‐channel TASK1 affects Oligodendroglial differentiation but not myelin restoration

The K_2P‐channel TASK1 affects Oligodendroglial differentiation but not myelin restoration

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TASK, TREK & Co.: a mutable potassium channel family for diverse tasks in the brain

Cited by 1 publication

References 58 publications

The K2P‐channel TASK1 affects Oligodendroglial differentiation but not myelin restoration

The K2P‐channel TASK1 affects Oligodendroglial differentiation but not myelin restoration

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The K_2P‐channel TASK1 affects Oligodendroglial differentiation but not myelin restoration

The K_2P‐channel TASK1 affects Oligodendroglial differentiation but not myelin restoration