Petrou S, Ordway R W, Hamilton J A, Walsh J V, Singer J J
Department of Physiology, University of Massachusetts Medical School, Worcester 01655.
J Gen Physiol. 1994 Mar;103(3):471-86. doi: 10.1085/jgp.103.3.471.
We determined the structural features necessary for fatty acids to exert their action on K+ channels of gastric smooth muscle cells. Examination of the effects of a variety of synthetic and naturally occurring lipid compounds on K+ channel activity in cell-attached and excised membrane patches revealed that negatively charged analogs of medium to long chain fatty acids (but not short chain analogs) as well as certain other negatively charged lipids activate the channels. In contrast, positively charged, medium to long chain analogs suppress activity, and neutral analogs are without effect. The key requirements for effective compounds seem to be a sufficiently hydrophobic domain and the presence of a charged group. Furthermore, those negatively charged compounds unable to "flip" across the bilayer are effective only when applied at the cytosolic surface of the membrane, suggesting that the site of fatty acid action is also located there. Finally, because some of the effective compounds, for example, the fatty acids themselves, lysophosphatidate, acyl Coenzyme A, and sphingosine, are naturally occurring substances and can be liberated by agonist-activated or metabolic enzymes, they may act as second messengers targeting ion channels.
我们确定了脂肪酸对胃平滑肌细胞钾通道发挥作用所必需的结构特征。研究各种合成和天然存在的脂质化合物对细胞贴附膜片和切除膜片中钾通道活性的影响后发现，中长链脂肪酸的带负电荷类似物（而非短链类似物）以及某些其他带负电荷的脂质可激活这些通道。相比之下，带正电荷的中长链类似物会抑制活性，而中性类似物则无作用。有效化合物的关键要求似乎是有足够的疏水结构域和带电基团的存在。此外，那些无法“翻转”穿过双层膜的带负电荷化合物只有在施加于膜的胞质表面时才有效，这表明脂肪酸的作用位点也位于此处。最后，由于一些有效化合物，例如脂肪酸本身、溶血磷脂酸、酰基辅酶A和鞘氨醇，都是天然存在的物质，并且可由激动剂激活的酶或代谢酶释放出来，它们可能作为靶向离子通道的第二信使发挥作用。
