DIRECT EFFECTS OF FATTY-ACIDS AND OTHER CHARGED LIPIDS ON ION-CHANNELACTIVITY IN SMOOTH-MUSCLE CELLS

A variety of fatty acids increase the activity of certain types of Kchannels, This effect is not dependent on the three enzymatic pathways that convert arachidonic acid to various bioactive oxygenated metabol ites. One type of K+ channel in toad stomach smooth muscle cell membra nes is activated by fatty acids and other single chain lipids which po ssess both a negatively charged head group and a sufficiently hydropho bic acyl chain, Neutral lipids have no effect on K+ channel activity, while positively charged lipids with a sufficiently hydrophobic acyl c hain suppress channel activity. Acyl Coenzyme A's, which do not flip a cross the bilayer, act only from the cytosolic surface of the membrane , suggesting that the binding site for channel activation is also loca ted there. This fatty acid-activated channel is also activated by memb rane stretch. Moreover, this mechanical response is either mediated or modulated by fatty acids. Thus, fatty acids and other charged single chain lipids may comprise another class of first or second messenger m olecules that target ion channels.