Effects of fatty acids on BK channels in GH(3) cells

Ca2+-activated K+ (BK) channels in GH(3) cells are activated by arachidonic acid (AA). Because cytosolic phospholipase A(2) can produce other unsatura ted free fatty acids (FFA), we examined the effects of FFA on BK channels i n excised patches. Control recordings were made at several holding potentia ls. The desired FFA was added to the bath solution, and the voltage paradig m was repeated. AA increased the activity of BK channels by 3.6 +/- 1.6-fol d. The cis FFA, palmitoleic, oleic, linoleic, linolenic, eicosapentaenoic, and the triple bond analog of AA, eicosatetraynoic acid, all increased BK c hannel activity, whereas stearic (saturated) or the trans isomers elaidic, linolelaidic, and linolenelaidic had no effect. The cis unsaturated FFA shi fted the open probability vs. voltage relationships to the left without a c hange in slope, suggesting no change in the sensitivity of the voltage sens or. Measurements of membrane fluidity showed no correlation between the cha nge of membrane fluidity and the change in BK channel activation. In additi on, AA effects on BK channels were unaffected in the presence of N-acetyl-c ysteine. Arachidonyl-CoA, a membrane impermeable analog of AA, activates ch annels when applied to the cytosolic surface of excised patches, suggesting an effect of FFAs from the cytosolic surface of BK channels. Our data impl y a direct interaction between cis FFA and the BK channel protein.