Regulation of adenylyl cyclase by membrane potential
Regulation of adenylyl cyclase by membrane potential
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DOI：
10.1074/jbc.273.42.27703
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发表时间：
1998-10-16
影响因子：
4.8
通讯作者：
Irvine, RF
中科院分区：
文献类型：
--
作者：
Cooper, DMF;Schell, MJ;Irvine, RF
哺乳动物腺苷酸环化酶具有12个跨膜结构域，并与某些类型的离子通道具有表面相似性。一些证据表明，细菌和海胆精子腺苷酸环化酶可以调节膜去极化。在本研究中，我们探讨了改变膜电位对急性钾离子去极化小脑颗粒细胞腺苷酸环化酶活性的影响。一个双相的刺激，然后抑制反应引起的细胞外[K]：[Na]比在细胞外Ca2+的情况下进行性增加。这种效应并不模拟在相同条件下引起的膜电位的线性增加。相反，似乎膜去极化打开L型（尼莫地平敏感）Ca2+通道，允许Na+进入，这直接刺激腺苷酸环化酶活性。短杆菌肽，它产生的孔是可渗透的一价阳离子，并同时消除膜电位，允许类似的刺激细胞外应用Na+。虽然结果表明小脑颗粒细胞腺苷酸环化酶对膜电位没有直接的敏感性，但它们确实表明，作为膜去极化的结果，Na+和Ca 2+的流入将升高cAMP水平。
Mammalian adenylyl cyclases possess 12 transmembrane-spanning domains and bear a superficial resemblance to certain classes of ion channels. Some evidence suggests that bacterial and sea urchin sperm adenylyl cyclases can be regulated by membrane depolarization. In the present study, we explored the effect of altering membrane potential on the adenylyl cyclase activity of cerebellar granule cells with acute potassium depolarization. A biphasic stimulatory and then inhibitory response is evoked by progressive increases in the extracellular [K]:[Na] ratio in the absence of-extracellular Ca2+. This effect does not mimic the linear increase in membrane potential elicited under the same conditions. Instead it appears as though membrane depolarization opens L-type (nimodipine-sensitive) Ca2+ channels, allowing the entry of Na+, which directly stimulates adenylyl cyclase activity. Gramicidin, which generates pores that are permeable to monovalent cations, and concurrently eliminates the membrane potential, permits a similar stimulation by extracellularly applied Na+. Although the results indicate no direct sensitivity of cerebellar granule cell adenylyl cyclase to membrane potential, they do demonstrate that, as a result of membrane depolarization, the influx of Na+, as well as Ca2+, will elevate cAMP levels.