Title: Arachidonic acid potently inhibits both postsynaptic-type Kv4.2 and presynaptic-type Kv1.4 IA potassium channels.

Authors: Plamena R Angelova, Wolfgang S Müller

Journal, date & volume: Eur. J. Neurosci., 2009 May , 29, 1943-50

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/19453640

Abstract
Arachidonic acid (AA) is a free fatty acid membrane-permeable second messenger that is liberated from cell membranes via receptor- and Ca(2+)-dependent events. We have shown previously that extremely low [AA](i) (1 pm) inhibits the postsynaptic voltage-gated K(+) current (I(A)) in hippocampal neurons. This inhibition is blocked by some antioxidants. The somatodendritic I(A) is mediated by Kv4.2 gene products, whereas presynaptic I(A) is mediated by Kv1.4 channel subunits. To address the interaction of AA with these alpha-subunits we studied the modulation of A-currents in human embryonic kidney 293 cells transfected with either Kv1.4 or Kv4.2 rat cDNA, using whole-cell voltage-clamp recording. For both currents 1 pm [AA](i) inhibited the conductance by > 50%. In addition, AA shifted the voltage dependence of inactivation by -9 (Kv1.4) and +6 mV (Kv4.2), respectively. Intracellular co-application of Trolox C (10 microm), an antioxidant vitamin E derivative, only slowed the effects of AA on amplitude. Notably, Trolox C shifted the voltage dependence of activation of Kv1.4-mediated I(A) by -32 mV. Extracellular Trolox for > 15 min inhibited the AA effects on I(A) amplitudes as well as the effect of intracellular Trolox on the voltage dependence of activation of Kv1.4-mediated I(A). Extracellular Trolox further shifted the voltage dependence of activation for Kv4.2 by +33 mV. In conclusion, the inhibition of maximal amplitude of Kv4.2 channels by AA can explain the inhibition of somatodendritic I(A) in hippocampal neurons, whereas the negative shift in the voltage dependence of inactivation apparently depends on other neuronal channel subunits. Both AA and Trolox potently modulate Kv1.4 and Kv4.2 channel alpha-subunits, thereby presumably tuning presynaptic transmitter release and postsynaptic somatodendritic excitability in synaptic transmission and plasticity.