Intrinsic oscillatory activity arising within the electrically coupled AII amacrine-ON cone bipolar cell network is driven by voltage-gated Na plus channels
Intrinsic oscillatory activity arising within the electrically coupled AII amacrine-ON cone bipolar cell network is driven by voltage-gated Na plus channels
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DOI：
10.1113/jphysiol.2011.225060
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发表时间：
2012-05-01
影响因子：
5.5
通讯作者：
Awatramani, Gautam B.
中科院分区：
文献类型：
--
作者：
Trenholm, Stuart;Borowska, Joanna;Awatramani, Gautam B.
在视网膜变性的rd 1小鼠模型中，光感受器的丧失导致视网膜ON锥双极细胞和AII无长突细胞的残余电耦合网络内的振荡活动（类似于10-20 Hz）。我们测试了超极化激活电流（I-H），电压门控Na+通道和间隙连接在介导这种振荡活动的作用。阻断I-h（1 mM Cs+）使网络超极化并增强活性，而拮抗电压依赖性Na+通道（1 μ M TTX）则废除了AII无长突-ON锥双极细胞网络中的振荡活性。电压门控Na+通道仅在AII无长突细胞中观察到，暗示这些细胞是活动的主要驱动因素。药理学解偶联的网络（200 μ M的甲酰胺酸（MFA））在所有细胞中的振荡，表明Na+通道发挥其影响在网络内的多种细胞类型。在野生型视网膜，闭塞的光感受器输入到双极细胞（10 μ M NBQX和50 μ M L-AP 4）导致轻度（类似于10 mV）超极化和AII无长突-ON锥双极细胞网络内的振荡活动的诱导。这些振荡与在rd 1视网膜中观察到的振荡具有相似的性质，这表明不需要主要的变性诱导的网络重新布线来触发自发振荡。最后，我们构建了一个简化的
In the rd1 mouse model for retinal degeneration, the loss of photoreceptors results in oscillatory activity (similar to 10-20 Hz) within the remnant electrically coupled network of retinal ON cone bipolar and AII amacrine cells. We tested the role of hyperpolarization-activated currents (I-h), voltage-gated Na+ channels and gap junctions in mediating such oscillatory activity. Blocking I-h (1 mM Cs+) hyperpolarized the network and augmented activity, while antagonizing voltage-dependent Na+ channels (1 mu M TTX) abolished oscillatory activity in the AII amacrine-ON cone bipolar cell network. Voltage-gated Na+ channels were only observed in AII amacrine cells, implicating these cells as major drivers of activity. Pharmacologically uncoupling the network (200 mu M meclofenamic acid (MFA)) blocked oscillations in all cells indicating that Na+ channels exert their influence over multiple cell types within the network. In wt retina, occluding photoreceptor inputs to bipolar cells (10 mu M NBQX and 50 mu M L-AP4) resulted in a mild (similar to 10 mV) hyperpolarization and the induction of oscillatory activity within the AII amacrine-ON cone bipolar cell network. These oscillations had similar properties to those observed in rd1 retina, suggesting that no major degeneration-induced network rewiring is required to trigger spontaneous oscillations. Finally, we constructed a simplified