STRUCTURAL REQUIREMENTS FOR CHARGED LIPID MOLECULES TO DIRECTLY INCREASE OR SUPPRESS K-MUSCLE CELLS - EFFECTS OF FATTY-ACIDS, LYSOPHOSPHATIDATE, ACYL COENZYME-A AND SPHINGOSINE( CHANNEL ACTIVITY IN SMOOTH)

We determined the structural features necessary for fatty acids to exe rt their action on K+ channels of gastric smooth muscle cells. Examina tion of the effects of a variety of synthetic and naturally occurring lipid compounds on K+ channel activity in cell-attached and excised me mbrane patches revealed that negatively charged analogs of medium to l ong chain fatty acids (but not short chain analogs) as well as certain other negatively charged lipids activate the channels. In contrast, p ositively charged, medium to long chain analogs suppress activity, and neutral analogs are without effect. The key requirements for effectiv e compounds seem to be a sufficiently hydrophobic domain and the prese nce of a charged group. Furthermore, those negatively charged compound s unable to ''flip'' across the bilayer are effective only when applie d at the cytosolic surface,of the membrane, suggesting that the site o f fatty acid action is also located there. Finally, because some of th e effective compounds, for example, the fatty acids themselves, lysoph osphatidate, acyl. Coenzyme A, and sphingosine, are naturally occurrin g substances and can be liberated by agonist-activated or metabolic en zymes, they may act as second messengers targeting ion channels.