THE EFFECT OF ARACHIDONIC-ACID ON THE M-CURRENT OF NG108-15 NEUROBLASTOMA X GLIOMA HYBRID-CELLS

The M current, I(M), a voltage-dependent non-inactivating K+ current, was recorded in NG108-15 neuroblastoma x glioma hybrid cells, using the whole-cell mode of the patch-clamp technique. We studied the effect of arachidonic acid, other fatty acids and inhibitors of the arachidonic acid metabolism. In relatively high concentrations (25-50 muM) arachidonic acid first increased and later decreased the current, I(h), which holds the membrane potential at -30 mV and mainly flows through open M channels. It shifted the midpoint potential, V(o), of the relation between M conductance, g(M), and membrane potential, V, to more negative values and decreased the maximum conductance g(M)BAR and the time constant tau(M). In smaller concentrations (5-10 muM) arachidonic acid merely decreased I(h) and g(M)BAR with little effect on V(o) and tau(M). Eicosatetraynoic acid and docosahexaenoic acid acted similarly to arachidonic acid whereas stearic acid had no effect. Of the three enzyme inhibitors studied, nordihydroguaiaretic acid acted similarly to arachidonic acid. i.e. caused a biphasic change in I(h). Indomethacin and quinacrine caused, respectively, a pure increase and a pure decrease of I(h) and g(M)BAR. Possible explanations are build-up of internally produced arachidonic acid, depletion of eicosanoid products or an inhibitory effect unrelated to arachidonic acid metabolism.