Effects of long-chain fatty acids on the channel activity of the nicotinic acetylcholine receptor.

We have analyzed the effect of free fatty acids on the function of the acetylcholine receptor (AChR) at the single-channel level, using the patch-clamp technique. Long-chain fatty acids, in the presence of albumin as a carrier, were applied to intact cells or to the cytoplasmic surface of excised membrane patches. In the latter case, AChR channels underwent immediate changes in their behaviour and only very brief opening events were apparent. This could be accounted for by a four-fold reduction in the channel mean open time, with no significant changes occurring in the conductance. An increase in the duration of intermediate closed intervals and a decrease in the burst duration were also observed. The modification appeared not to be critically dependent on the degree of saturation of fatty acyl chains. Addition of free fatty acids in the absence of albumin, as well as treatment of the excised membrane patches with phospholipase A2, resulted in complete inhibition of AChR channel activity. In intact cells, fatty acids could reach and affect AChR channels in the plasmalemma under the patch pipette when added from outside the patch-clamped area. The fatty acid-modified AChR was still able to undergo desensitization. The open channel probability was higher than 0.8 for 100 microM agonist, decreasing to 0.4 in the fatty acid-modified receptors. The results are discussed within the framework of the hypothesis that some lipophilic compounds exert their action on the AChR-lipid interface (the "annulus") (see Barantes, 1993).