Schweitzer P, Madamba S, Siggins G R
Research Institute of Scripps Clinic, Department of Neuropharmacology, La Jolla, California 92037.
Nature. 1990 Aug 2;346(6283):464-7. doi: 10.1038/346464a0.
The M-current (IM) is a time- and voltage-dependent K+ current that persists at slightly depolarized membrane potentials. IM is reduced by muscarinic cholinergic agonists and certain peptides, and is thought to be responsible in part for the slow and late slow excitatory postsynaptic potentials in sympathetic neurons. Recently, we reported that IM in hippocampal neurons was also augmented by somatostatin-14 and -28 suggesting that two different receptors reciprocally regulate one neuronal channel type. Muscarinic effects on IM may be mediated by various components of the phosphatidylinositol phosphate pathway. We now report the involvement of a different second messenger pathway, that generated by phospholipase A2, in the somatostatin-induced augmentation of IM in hippocampal cells. This pathway generates arachidonic acid from which leukotrienes can be produced by lipoxygenases. We find that the IM-augmenting effects of somatostatin are abolished by two substances that can inhibit phospholipase A2, quinacrine and 4-bromophenacyl bromide, and that both arachidonic acid and leukotriene C4 mimic the effects of somatostatin-14 on hippocampal pyramidal neurons in vitro. Arachidonic and somatostatin effects are blocked by a lipoxygenase inhibitor, implicating an arachidonic acid metabolite, perhaps a leukotriene, in the somatostatin effect.
M电流（IM）是一种依赖时间和电压的钾离子电流，在膜电位轻度去极化时持续存在。M电流可被毒蕈碱型胆碱能激动剂和某些肽类所减弱，被认为部分介导了交感神经元中缓慢及延迟的慢兴奋性突触后电位。最近，我们报道海马神经元中的M电流也可被生长抑素-14和-28增强，这表明两种不同的受体相互调节一种神经元通道类型。毒蕈碱对M电流的作用可能由磷脂酰肌醇磷酸途径的多种成分介导。我们现在报道，一种由磷脂酶A2产生的不同的第二信使途径参与了生长抑素诱导的海马细胞M电流增强。该途径从花生四烯酸生成白三烯，花生四烯酸可由脂氧合酶产生白三烯。我们发现，生长抑素增强M电流的作用可被两种能抑制磷脂酶A2的物质——喹吖因和4-溴苯甲酰溴所消除，并且花生四烯酸和白三烯C4在体外均可模拟生长抑素-14对海马锥体神经元的作用。花生四烯酸和生长抑素的作用可被脂氧合酶抑制剂阻断，这表明花生四烯酸代谢产物，可能是一种白三烯，参与了生长抑素的作用。
