Figure 12.

Inhibition of ATP-dependent gating by free fatty acids in neurons, and in oocytes expressing GIRK. Inside-out patches were formed and membrane potential held at −60 mV. (A) 5-HT was used as the agonist. Reversible inhibition by linoleic acid of the ATP-dependent gating of the K_ACh channels in an adult rat hippocampal neuron is shown with accompanying expanded tracings. (B) The cardiac (GIRK1/4) form of the K_ACh channel subunits were expressed at low levels in Xenopus oocytes and activated by βγ (50 nM). ATP produced long-lived openings as in atrial cells. Oleic acid, AA, and fatty acid–free albumin (100 μg/ml) were applied as indicated. (C) The neuronal (GIRK1/2) form of the K_ACh channel subunits were expressed at low levels in Xenopus oocytes and activated by βγ (50 nM). After adding ATP, AA and linoleic acids were applied separately. Albumin was used to reverse the effect of AA. Expanded current tracings show the effect of free fatty acids on the kinetics of channel openings. (D) Summary of changes in relative channel activity and open-time constants determined from above experiments is shown. *Significant difference from the control values obtained in the absence of fatty acid (P < 0.05). Open time constants were calculated from the transition rates. Each bar is the mean ± SD of four determinations.