Ca2+/cAMP-Sensitive Covariation of IA and IH Voltage Dependences Tunes Rebound Firing in Dopaminergic Neurons
Ca2+/cAMP-Sensitive Covariation of IA and IH Voltage Dependences Tunes Rebound Firing in Dopaminergic Neurons
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DOI：
10.1523/jneurosci.5297-11.2012
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发表时间：
2012-02-08
影响因子：
5.3
通讯作者：
Goaillard, Jean-Marc
中科院分区：
文献类型：
--
作者：
Amendola, Julien;Woodhouse, Adele;Goaillard, Jean-Marc
离子通道的表达水平已被证明在神经元之间的变化范围为三到四倍，尽管不同通道的表达可能在同一神经元中强烈相关。我们证明变异和共变也适用于离子通道的生物物理性质。我们发现，在大鼠黑质致密部多巴胺能神经元中，a型（I-A）和h型（I-H）电流的电压依赖性表现出高度的细胞间变异性，尽管它们在这些细胞中密切相关。我们的数据还表明，这种电压依赖性的细胞间协变性对细胞质cAMP和钙水平敏感。最后，利用动态箝位，我们证明了共变的I-A和I-H电压依赖性增加了回弹射击的动态范围，而共变它们的振幅对回弹射击具有稳态效应。我们提出离子通道电压依赖性的共变代表了一种灵活和节能的调节神经元放电的方式。
The level of expression of ion channels has been demonstrated to vary over a threefold to fourfold range from neuron to neuron, although the expression of distinct channels may be strongly correlated in the same neurons. We demonstrate that variability and covariation also apply to the biophysical properties of ion channels. We show that, in rat substantia nigra pars compacta dopaminergic neurons, the voltage dependences of the A-type (I-A) and H-type (I-H,) currents exhibit a high degree of cell-to-cell variability, although they are strongly correlated in these cells. Our data also demonstrate that this cell-to-cell covariability of voltage dependences is sensitive to cytosolic cAMP and calcium levels. Finally, using dynamic clamp, we demonstrate that covarying I-A and I-H, voltage dependences increases the dynamic range of rebound firing while covarying their amplitudes has a homeostatic effect on rebound firing. We propose that the covariation of voltage dependences of ion channels represents a flexible and energy-efficient way of tuning firing in neurons.