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.