Koch K W, Cook N J, Kaupp U B
Abteilung Biophysik, Universität Osnabrück, Federal Republic of Germany.
J Biol Chem. 1987 Oct 25;262(30):14415-21.
cGMP cooperatively activates a cation-selective channel in vertebrate photoreceptors probably by direct binding to a membrane receptor (Fesenko, E. E., Kolesnikov, S. S., and Lyubarsky, A.L. (1985) Nature 313, 310-313). We have recently described the existence of a similar channel in photoreceptor disc membranes (Koch, K. W., and Kaupp, U. B. (1985) J. Biol. Chem. 260, 6788-6800). In this paper we report that the cGMP-dependent channel in the disc membrane of outer segments exists in at least two forms of different cGMP sensitivity and pharmacological behavior. One form has a low Km value of activation by cGMP (25 microM), and it is not blocked by l-cis-diltiazem. The other form has a high Km value (170 microM) and is blocked by this drug. Both channel forms are cooperatively activated by cGMP (Hill coefficient n = 2.0-3.5), suggesting that the channel may have a cGMP receptor that can bind at least three, and possibly four, molecules of cGMP. In the presence of cGMP, the open state of both channel forms inactivates to a weakly or nonconductive state (cf. Puckett, K. L., and Goldin, S. M. (1986) Biochemistry 25, 1739-1746). A mixed population of different forms of the cGMP-dependent channel may explain the variable numbers reported for the Michaelis constant Km for the channel activation by cGMP and the cooperativity n.
环磷酸鸟苷（cGMP）可能通过直接与膜受体结合，协同激活脊椎动物光感受器中的阳离子选择性通道（费先科，E.E.，科列斯尼科夫，S.S.，柳巴尔茨基，A.L.（1985年）《自然》313卷，310 - 313页）。我们最近报道了在光感受器盘膜中存在类似的通道（科赫，K.W.，考普，U.B.（1985年）《生物化学杂志》260卷，6788 - 6800页）。在本文中我们报告，外段盘膜中的cGMP依赖性通道至少以两种具有不同cGMP敏感性和药理行为的形式存在。一种形式对cGMP激活的米氏常数（Km）值较低（25微摩尔），并且不受l - 顺式地尔硫䓬阻断。另一种形式具有较高的Km值（170微摩尔），并被这种药物阻断。两种通道形式均被cGMP协同激活（希尔系数n = 2.0 - 3.5），这表明该通道可能具有一个能结合至少三个，也可能四个cGMP分子的cGMP受体。在有cGMP存在的情况下，两种通道形式的开放状态都会失活至弱导电或不导电状态（参见帕克特，K.L.，戈尔丁，S.M.（1986年）《生物化学》25卷，1739 - 1746页）。cGMP依赖性通道不同形式的混合群体可能解释了报道的关于该通道被cGMP激活的米氏常数Km和协同性n的可变数值。
