Thursday, 1 June 2017

Potassium overload and oligodendrocyte death

To continue on the theme that too much potassium is bad for oligodendrocyes and probably other cells

http://multiple-sclerosis-research.blogspot.com/2017/05/gaba-and-remyelination-its-confusing-i.html

http://multiple-sclerosis-research.blogspot.com/2017/05/damaging-cholesterol.html

 Oligodendrocytes down regulate most of their potassium channels

However one channel reported to be of interest is the TASK-1 channel. This also known as Potassium channel subfamily K member 3 encoded by the KCNK3 (or K2P3.1), one of the members of the superfamily of potassium channel proteins containing two pore-forming P domains. 

K2P3.1 is an outwardly rectifying channel that is sensitive to changes in extracellular pH (acidity-alkalinitiy) and is inhibited by low pH (acidity).  It is known as a "Leak" channel that sets the membrane potential (the difference in voltage between the outside and inside of the cell). Potassium tends to leak outwards. However, when there is a strong depolarising signal the potassium will move inwards to increase the potassium. We saw the other day that this can be bad news. 

Hawkins V, Butt A. TASK-1 channels in oligodendrocytes: a role in ischemia mediated disruption. Neurobiol Dis. 2013 Jul;55:87-94

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.

So in this situation when you have ischaemia/ischemia (or lack of blood supply and lack of oxygen) and damage to oligodendrocytes, they found that if they block TASK-1 potassium channels they can limit oligdendrocyte death.

The problem is that they used anandamide (endogenous cannabinoid) and methanandamide (a metabolically stable version of anandamide that is not destroyed in the body like anadamide is within a few minutes. However this says that anandamide can save oligos. It can also save nerves, but that's another story, which we tell you later.

However, is this how anandamide works?...after all its a dirty drug, with more than one target.

5 comments:

  1. Must I stop eating dried bananas then? I estimate I eat the equivalent of about 30 in a sitting. I thought they made me feel good. Gorilla power.

    ReplyDelete
    Replies
    1. I think this is a stroke or short of blood suply situation

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    2. Does ms pathogenesis have hypoxic/ischemic episodes?
      Thanks
      luis

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    3. dietry potassium is not the same as potassium loading in pathology

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    4. Thanks for the reassurance - more dried bananas for me.

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