Eicosatetraynoic acid (ETYA), a non-metabolizable analogue of arachidonic acid, blocks the fast-inactivating potassium current of rat pituitary melanotrophs

The effects of arachidonic acid (5,8,11,14-eicosatetraenoic acid, AA) and 5,8,11,14-eicosatetraynoic acid (ETYA), a non-metabolizable analogue of AA, were examined on the transient [I(K)(f)] and the delayed rectifier-like [I(K)(S)] voltage-gated potassium currents in rat pituitary melanotrophs. The main questions addressed were whether AA and ETYA blocked I(K)(f) and if any blocking action was specific. Macroscopic currents were measured using the patch clamp technique. Bath application of 20 microM AA reduced I(K)(f), however, the degree of the block varied between cells. In contrast, ETYA consistently inhibited I(K)(f). Fitting of the charge transfer or the peak current amplitude yielded KD estimates for ETYA of 1.2 microM and 3.3 microM, respectively. The reduction by ETYA of peak I(K)(f) was always associated with an increased rate of current decay, but there was no detectable change of the kinetics of activation. ETYA caused a small left shift of the I(K)(f) steady-state inactivation curve and significantly slowed recovery from inactivation. At 20 microM, ETYA also reduced I(K)(s), indicating that it is not specific. The possibility that ETYA acts as an open-channel blocker is discussed.