The Cav3-Kv4 Complex Acts as a Calcium Sensor to Maintain Inhibitory Charge Transfer during Extracellular Calcium Fluctuations
The Cav3-Kv4 Complex Acts as a Calcium Sensor to Maintain Inhibitory Charge Transfer during Extracellular Calcium Fluctuations
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DOI：
10.1523/jneurosci.5384-12.2013
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发表时间：
2013-05-01
影响因子：
5.3
通讯作者：
Turner, Ray W.
中科院分区：
文献类型：
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作者：
Anderson, Dustin;Engbers, Jordan D. T.;Turner, Ray W.
突触传递和神经元兴奋性依赖于细胞外钙离子浓度([Ca](O))，然而，重复突触输入会降低许多脑区的[Ca](O)。在小脑分子层，突触输入使星状细胞间神经元和浦肯野细胞树突附近的[Ca](O)降低达0.4 mm。面对钙梯度的快速变化，用来维持网络兴奋性和浦肯野细胞输出的机制仍然是一个谜。在此，我们在SD大鼠的体外脑片制备中使用单片和双片记录来研究生理性的[Ca](O)降低对小脑星状细胞兴奋性的影响及其对浦肯野细胞的抑制调节。我们发现，在星状细胞中表达的Ca(V)3-K(V)4离子通道复合体作为一种钙传感器，通过动态调整星状细胞的输出来维持到浦肯野细胞的抑制性电荷转移，以响应[Ca](O)的下降。因此，Ca(V)3-K(V)4复合体能够在[Ca](O)波动期间对浦肯野细胞的抑制性输入进行适应性调节，提供一种动态平衡控制机制来调节浦肯野细胞在重复传入活动中的兴奋性。
Synaptic transmission and neuronal excitability depend on the concentration of extracellular calcium ([Ca](o)), yet repetitive synaptic input is known to decrease [Ca](o) in numerous brain regions. In the cerebellar molecular layer, synaptic input reduces [Ca](o) by up to 0.4 mM in the vicinity of stellate cell interneurons and Purkinje cell dendrites. The mechanisms used to maintain network excitability and Purkinje cell output in the face of this rapid change in calcium gradient have remained an enigma. Here we use single and dual patch recordings in an in vitro slice preparation of Sprague Dawley rats to investigate the effects of physiological decreases in [Ca](o) on the excitability of cerebellar stellate cells and their inhibitory regulation of Purkinje cells. We find that a Ca(v)3-K(v)4 ion channel complex expressed in stellate cells acts as a calcium sensor that responds to a decrease in [Ca](o) by dynamically adjusting stellate cell output to maintain inhibitory charge transfer to Purkinje cells. The Ca(v)3-K(v)4 complex thus enables an adaptive regulation of inhibitory input to Purkinje cells during fluctuations in [Ca](o), providing a homeostatic control mechanism to regulate Purkinje cell excitability during repetitive afferent activity.