Modulation of Ion Channels by Arachidonate

Now that we have qualified, at least in first approximation, what we mean by endogenous free arachidonate levels, we may turn to our first example of the biological effects produced by the administration of this fatty acid as a pharmacological agent. 

Modulation through protein kinase activation arachidonate - 

Singer and colleagues studied the effect of non-esterified arachidonate on potassium channels by dissolving the fatty acid in the bathing medium and perfusing it on the inside of the smooth muscle membrane (in the inside-out configuration) or on its outside (in the outside-out configuration). In either case, they found that application of micromolar concentrations of the fatty acid would cause the activation of a potassium-selective channel (Fig. 3.6). This effect was not mediated by the formation of 

Beside arachidonate, a large number of hydrophobic molecules bearing a negatively charged group were found to increase potassium channel activity by contrast, positively charged lipids were found to close the potassium channel. The structures of some lipid molecules shown to activate potassium channels in toad smooth 

David Attwell and collaborators, at the University College in London, found that arachidonate increases, in cerebellar granule cells, the current flowing through activated NMDA channels, whereas it reduces the current through non-NMDA channels.This potentiating effect appears to be produced by a direct interaction of the fatty acid with the channel molecule or with its lipid environment, as it is not prevented by inhibitors of arachidonic acid metabolism or protein kinase activity. Interestingly, the NMDA receptor contains a domain of 131 amino acid residues that is 

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Meves H. Modulation of ion channels by arachidonic acid. Prog Neurobiol 1994 43 175-186. 

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