Calcium modulation of ligand affinity in the cyclic GMP-gated ion channels of cone photoreceptors
Calcium modulation of ligand affinity in the cyclic GMP-gated ion channels of cone photoreceptors
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DOI：
10.1085/jgp.110.5.515
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发表时间：
1997-11-01
影响因子：
3.8
通讯作者：
Korenbrot, JI
中科院分区：
文献类型：
--
作者：
Hackos, DH;Korenbrot, JI
为了研究cGMP门控的loll通道在视锥细胞中激活的调节，我们测量了从条纹低音视网膜分离的单个视锥细胞外节分离的膜斑的电流。这些通道对cGMP激活的敏感性取决于暴露于膜细胞质表面二价阳离子的历史。在20 μ M的Ca++和100 μ M的Mg++切除后，维持在补丁，电流幅度依赖于cGMP是很好地描述了希尔方程与K-1/2，激活一半的最大电流，86 μ M和协同指数，n，为2.57的平均值所需的浓度。将贴片暴露于不含二价阳离子的溶液中不可逆地增加cGMP敏感性; K-1/2的平均值变为58.5 μ M，n变为1.8。cGMP敏感性的变化不影响离子通道的其他功能参数，如一价和二价阳离子的相互作用和渗透。cGMP激活的调节依赖于内源性因子的作用，当Ca++浓度降低到1 μ M以下时，内源性因子逐渐从通道中解离。内源性调节剂的活性不能很好地被外源性添加的钙调蛋白模拟，尽管这种蛋白质与内源性调节剂竞争共同的结合位点。因此，视锥细胞中cGMP亲和力的调节取决于一种可能不是钙调素的未鉴定分子的活性。
To investigate modulation of the activation of cGMP-gated loll channels in cone photoreceptors, ive measured currents in membrane patches detached from the outer segments of single cones isolated from striped bass retina. The sensitivity of these channels to activation by cGMP depends on the history of exposure to divalent cations of the membrane's cytoplasmic surface. In patches maintained in 20 mu M Ca++ and 100 mu M Mg++ after excision, the current amplitude dependence on cGMP is well described by a Hill equation with average values of K-1/2, the concentration necessary to activate half the maximal current, of 86 mu M and a cooperativity index, n, of 2.57. Exposing the patch to a solution free of divalent cations irreversibly increases the cGMP sensitivity; the average value of K-1/2 shifts to 58.5 mu M and n shifts to 1.8. Changes in cGMP sensitivity do not affect other functional parameters of the ion channels, such as the interaction and permeation of mono-and divalent cations. Modulation of cGMP activation depends on the action of an endogenous factor that progressively dissociates from the channel as Ca++ concentration is lowered below 1 mu M. The activity of the endogenous modulator is not well mimicked by exogenously added calmodulin, although this protein competes with the endogenous modulator for a common binding site. Thus, the modulation of cGMP affinity in cones depends on the activity of an unidentified molecule that may not be calmodulin.