Role of Small Conductance Ca2+-Activated K+ Channels in Controlling CA1 Pyramidal Cell Excitability
Role of Small Conductance Ca2+-Activated K+ Channels in Controlling CA1 Pyramidal Cell Excitability
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DOI：
10.1523/jneurosci.0936-14.2014
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发表时间：
2014-06-11
影响因子：
5.3
通讯作者：
Yaari, Yoel
中科院分区：
文献类型：
--
作者：
Chen, Shmuel;Benninger, Felix;Yaari, Yoel
小电导Ca ~（2+）激活的K ~+（SK或K（Ca）~（2+））通道广泛表达于中枢神经系统。在几种类型的神经元中，这些通道在重复放电期间被激活，导致早期尖峰频率适应。在CA 1锥体细胞中，树突棘中的SK通道被证明调节突触传递。然而，在胞体中的功能SK通道的存在及其在控制这些神经元的内在放电中的作用一直存在争议。使用全细胞电压钳和电流钳记录在急性海马切片和不可逆和可逆SK通道阻滞剂的局部应用，我们提供的证据表明，功能SK通道表达在成年大鼠CA 1锥体细胞的胞体和近端树突。虽然这些通道可以产生中等持续时间的后超极化电流，但它们在控制这些神经元的内在兴奋性方面仅起辅助作用，继发于低电压激活的非失活K（V）7/M通道。只要K（V）7/M通道是有效的，在重复放电过程中激活SK通道并不明显影响CA 1锥体细胞的锋电位输出。然而，当K（V）7/M通道活动受到损害时，SK通道激活会显着且独特地减少这些神经元的锋电位输出。因此，近端SK通道提供了对抗内在超兴奋性的“第二道防线”，这可能在K（V）7/M通道活性受损的多种情况下发挥作用，例如低摩尔浓度。
Small-conductance Ca2(+)-activated K+ (SK or K(Ca)2) channels are widely expressed in the CNS. In several types of neurons, these channels were shown to become activated during repetitive firing, causing early spike frequency adaptation. In CA1 pyramidal cells, SK channels in dendritic spines were shown to regulate synaptic transmission. However, the presence of functional SK channels in the somata and their role in controlling the intrinsic firing of these neurons has been controversial. Using whole-cell voltage-clamp and current-clamp recordings in acute hippocampal slices and focal applications of irreversible and reversible SK channel blockers, we provide evidence that functional SK channels are expressed in the somata and proximal dendrites of adult rat CA1 pyramidal cells. Although these channels can generate a medium duration afterhyperpolarizing current, they play only an auxiliary role in controlling the intrinsic excitability of these neurons, secondary to the low voltage-activating, noninactivating K(V)7/M channels. As long as K(V)7/M channels are operative, activation of SK channels during repetitive firing does not notably affect the spike output of CA1 pyramidal cells. However, when K(V)7/M channel activity is compromised, SK channel activation significantly and uniquely reduces spike output of these neurons. Therefore, proximal SK channels provide a "second line of defense" against intrinsic hyperexcitability, which may play a role in multiple conditions in which K(V)7/M channels activity is compromised, such as hyposmolarity.