ARACHIDONIC-ACID ACTIVATION OF A NEW FAMILY OF K+ CHANNELS IN CULTURED RAT NEURONAL CELLS
ARACHIDONIC-ACID ACTIVATION OF A NEW FAMILY OF K+ CHANNELS IN CULTURED RAT NEURONAL CELLS
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DOI：
10.1113/jphysiol.1995.sp020693
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发表时间：
1995-05-01
影响因子：
5.5
通讯作者：
MATHIASEN, JR
中科院分区：
文献类型：
--
作者：
KIM, DH;SLADEK, CD;MATHIASEN, JR
1.研究了大鼠中脑和下丘脑神经元细胞中花生四烯酸激活的K+通道的存在和性质.花生四烯酸产生浓度依赖性（5-50 μ M）和可逆的全细胞电流激活.花生四烯酸作用于离体细胞膜的胞浆侧或胞外侧，可使三种类型的通道开放，其电流-电压关系分别为轻微的外向整流、内向整流和线性，在+60 mV时的单通道斜率电导分别为143、45和52 pS.所有三个电流都是K+选择性的，并且被2 mM Ba 2+阻断，但不被其他K+通道阻断剂如四乙基氯化铵、4-氨基吡啶和奎尼丁阻断。外向整流电流和内向整流电流均具有轻微的电压依赖性，去极化电位越高，通道活性越高.花生四烯酸激活的K+通道与环氧合酶和脂氧合酶抑制剂（吲哚美辛和去甲二氢愈创木酸）处理的细胞，表明花生四烯酸本身可以直接激活通道。花生四烯酸的醇和甲酯衍生物不能激活K+通道，表明炭化的艾德羧基对激活是重要的。bbb6.某些不饱和脂肪酸（亚油酸、亚麻酸和二十二碳六烯酸），但不饱和脂肪酸（肉豆蔻酸、棕榈酸、硬脂酸），也可逆地激活所有三种类型的K+通道。所有三个K+通道都通过施加到膜上的压力激活（即通道是拉伸敏感的），其中半最大压力类似于18 mmHg。K+通道不被100 μ M GdCl 3.8阻断。细胞内pH值的降低（在5.6-7.2的范围内）引起通道活性的可逆的、pH依赖性的增加，无论通道最初是由花生四烯酸还是拉伸激活的。据报道，谷氨酸是一种在纹状体神经元中产生花生四烯酸的神经递质，当在细胞贴附的贴片中细胞外应用时，不会引起K+通道的激活。有人建议，这里描述的K+通道属于一个不同的家庭的离子通道，激活脂肪酸或膜拉伸。虽然这些K+通道的生理作用尚不清楚，但它们可能参与细胞过程，如细胞体积调节和缺血诱导的K+损失升高。
1. The presence and properties of K+ channels activated by arachidonic acid were studied in neuronal cells cultured from the mesencephalic and hypothalamic areas of rat brain.2. Arachidonic acid produced a concentration-dependent (5-50 mu M) and reversible activation of whole-cell currents.3. In excised membrane patches, arachidonic acid applied to the cytoplasmic or extracellular side of the membrane caused opening of three types of channels whose current-voltage relationships were slightly outwardly rectifying, inwardly rectifying and linear, and whose single channel slope conductances at +60 mV were 143, 45 and 52 pS, respectively.4. All three currents were K+ selective and blocked by 2 mM Ba2+ but not by other K+ channel blockers such as tetraethylammoninm chloride, 4-aminopyridine and quinidine. The outwardly and inwardly rectifying currents were slightly voltage dependent with higher channel activity at more depolarized potentials.5. Arachidonic acid activated the K+ channels in cells treated with cyclo-oxygenase and lipoxygenase inhibitors (indomethacin and nordihydroguaiaretic acid), indicating that arachidonic acid itself can directly activate the channels. Alcohol and methyl ester derivatives of arachidonic acid failed to activate the K+ channels, indicating that the chars ed carboxyl group is important for activation. bbbb6. Certain unsaturated fatty acids (linoleic, linolenic and docosahexaenoic acids), but not saturated fatty acids (myristic, palmitic, stearic acids), also reversibly activated all three types of K+ channel.7. All three K+ channels were activated by pressure applied to the membrane (i.e. channels were stretch sensitive) with a half-maximal pressure of similar to 18 mmHg. The K+ channels were not blocked by 100 mu M GdCl3.8. A decrease in intracellular pH (over the range 5.6-7.2) caused a reversible, pH-dependent increase in channel activity whether the channel was initially activated by arachidonic acid or stretch.9. Glutamate, a neurotransmitter reported to generate arachidonic acid in striatal neurons, did not cause activation of the K+ channels when applied extracellularly in cell-attached patches.10. It is suggested that the K+ channels described here belong to a distinct family of ion channels that are activated by either fatty acids or membrane stretch. Although the physiological roles of these K+ channels are not yet known, they may be involved in cellular processes such as cell volume regulation and ischaemia-induced elevation of K+ loss.