Cooper D M, Schell M J, Thorn P, Irvine R F
Department of Pharmacology, University of Cambridge, Cambridge CB2 1QJ, United Kingdom.
J Biol Chem. 1998 Oct 16;273(42):27703-7. doi: 10.1074/jbc.273.42.27703.
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.
哺乳动物腺苷酸环化酶具有12个跨膜结构域，与某些类型的离子通道表面相似。一些证据表明，细菌和海胆精子的腺苷酸环化酶可受膜去极化调节。在本研究中，我们利用急性钾去极化探讨了改变膜电位对小脑颗粒细胞腺苷酸环化酶活性的影响。在无细胞外Ca2+的情况下，细胞外[K]：[Na]比值逐渐增加会引发双相刺激然后抑制反应。这种效应并不模拟在相同条件下引发的膜电位线性增加。相反，似乎膜去极化会打开L型（尼莫地平敏感）Ca2+通道，使Na+进入，直接刺激腺苷酸环化酶活性。短杆菌肽可形成对单价阳离子通透的孔，并同时消除膜电位，它能使细胞外施加的Na+产生类似的刺激作用。尽管结果表明小脑颗粒细胞腺苷酸环化酶对膜电位无直接敏感性，但确实证明，由于膜去极化，Na+以及Ca2+的内流会提高环磷酸腺苷（cAMP）水平。
