Peretz A, Abitbol I, Sobko A, Wu C F, Attali B
Neurobiology Department, Weizmann Institute of Science, Rehovot 76100, Israel.
J Neurosci. 1998 Nov 15;18(22):9153-62. doi: 10.1523/JNEUROSCI.18-22-09153.1998.
Light activation of Drosophila photoreceptors leads to the generation of a depolarizing receptor potential via opening of transient receptor potential and transient receptor potential-like cationic channels. Counteracting the light-activated depolarizing current are two voltage-gated K+ conductances, IA and IK, that are expressed in these sensory neurons. Here we show that Drosophila photoreceptors IA and IK are regulated by calcium-calmodulin (Ca2+/calmodulin) via a Ca2+/calmodulin-dependent protein kinase (CaM kinase), with IK being far more sensitive than IA. Inhibition of Ca2+/calmodulin by N-(6 aminohexyl)-5-chloro-1-naphthalenesulfonamide or trifluoperazine markedly reduced the K+ current amplitudes. Likewise, inhibition of CaM kinases by KN-93 potently depressed IK and accelerated its C-type inactivation kinetics. The effect of KN-93 was specific because its structurally related but functionally inactive analog KN-92 was totally ineffective. In Drosophila photoreceptor mutant ShKS133, which allows isolation of IK, we demonstrate by current-clamp recording that inhibition of IK by quinidine or tetraethylammonium increased the amplitude of the photoreceptor potential, depressed light adaptation, and slowed down the termination of the light response. Similar results were obtained when CaM kinases were blocked by KN-93. These findings place photoreceptor K+ channels as an additional target for Ca2+/calmodulin and suggest that IK is well suited to act in concert with other components of the signaling machinery to sharpen light response termination and fine tune photoreceptor sensitivity during light adaptation.
果蝇光感受器的光激活通过瞬时受体电位和类瞬时受体电位阳离子通道的开放导致去极化受体电位的产生。在这些感觉神经元中表达的两种电压门控钾离子电导IA和IK可抵消光激活的去极化电流。在这里，我们表明果蝇光感受器的IA和IK受钙调蛋白（Ca2+/钙调蛋白）通过钙调蛋白依赖性蛋白激酶（CaM激酶）的调节，其中IK比IA敏感得多。用N-(6-氨基己基)-5-氯-1-萘磺酰胺或三氟拉嗪抑制Ca2+/钙调蛋白可显著降低钾离子电流幅度。同样，用KN-93抑制CaM激酶可有效抑制IK并加速其C型失活动力学。KN-93的作用具有特异性，因为其结构相关但功能无活性的类似物KN-92完全无效。在果蝇光感受器突变体ShKS133中，该突变体可分离出IK，我们通过电流钳记录证明，奎尼丁或四乙铵对IK的抑制增加了光感受器电位的幅度，抑制了光适应，并减缓了光反应的终止。当用KN-93阻断CaM激酶时也获得了类似的结果。这些发现将光感受器钾离子通道作为Ca2+/钙调蛋白的另一个靶点，并表明IK非常适合与信号传导机制的其他成分协同作用，以增强光反应终止并在光适应过程中微调光感受器的敏感性。
