The Voltage-Gated Anion Channels Encoded by clh-3 Regulate Egg Laying in C. elegans by Modulating Motor Neuron Excitability
The Voltage-Gated Anion Channels Encoded by clh-3 Regulate Egg Laying in C. elegans by Modulating Motor Neuron Excitability
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DOI：
10.1523/jneurosci.3112-13.2014
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发表时间：
2014-01-15
影响因子：
5.3
通讯作者：
Schafer, William R.
中科院分区：
文献类型：
--
作者：
Branicky, Robyn;Miyazaki, Hiroaki;Schafer, William R.
ClC-2是一种超极化激活的内向整流性氯离子通道。虽然ClC-2通道的特性已经被很好地描述，但它在体内的功能还不是很清楚。我们发现由秀丽线虫ClC-2同源基因CLH-3编码的通道调节自发活跃的两性特异性神经元(HSN)的活动，而HSN控制产卵行为。我们在CLH-3中发现了一个功能增益突变，它增加了通道的活性。该突变抑制产卵，并通过降低HSN的兴奋性来抑制HSN的活性。相反，CLH-3功能缺失突变导致错误的产卵和HSN兴奋性的增加，表明这些通道通过限制HSN的兴奋性来调节产卵。GABA(A)受体介导的HSN抑制不需要CLH-3编码的通道。然而，它们需要较低的细胞内氯来抑制HSN，这表明它们通过介导氯内流直接抑制兴奋性。这种CLH-3依赖的调节机制可能在其他驱动力有利于氯离子内流的神经元中保守。
CLC-2 is a hyperpolarization-activated, inwardly rectifying chloride channel. Although the properties of the CLC-2 channel have been well characterized, its function in vivo is not well understood. We have found that channels encoded by the Caenorhabditis elegans CLC-2 homolog clh-3 regulate the activity of the spontaneously active hermaphrodite-specific neurons (HSNs), which control the egg-laying behavior. We identified a gain-of-function mutation in clh-3 that increases channel activity. This mutation inhibits egg laying and inhibits HSN activity by decreasing its excitability. Conversely, loss-of-function mutations in clh-3 lead to misregulated egg laying and an increase in HSN excitability, indicating that these channels modulate egg laying by limiting HSN excitability. clh-3-encoded channels are not required for GABA(A)-receptor-mediated inhibition of the HSN. However, they require low intracellular chloride for HSN inhibition, indicating that they inhibit excitability directly by mediating chloride influx. This mechanism of CLH-3-dependent modulation may be conserved in other neurons in which the driving force favors chloride influx.