Specific contribution of human T-type calcium channel isotypes (α1G, α1H and α1I) to neuronal excitability
Specific contribution of human T-type calcium channel isotypes (α1G, α1H and α1I) to neuronal excitability
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DOI：
10.1113/jphysiol.2001.013269
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发表时间：
2002-04-01
影响因子：
5.5
通讯作者：
Lory, P
中科院分区：
文献类型：
--
作者：
Chemin, J;Monteil, A;Lory, P
在几种类型的神经元中，放电是特定类别离子通道产生的固有特性。低电压激活的 T 型钙通道（T 通道）通过膜的小去极化激活，可以产生突发放电和起搏器活动。在这里，我们研究了克隆的人类 T 通道亚基对神经元兴奋性的具体贡献。使用瞬时转染人 α(1G) (Cav3.1)、α(1H) (Cav3.2) 和所有 (Cav3.3) 亚基的 HEK-293 细胞，我们描述了这些同种型之间在生物物理特性方面的显着差异，这在动作电位钳研究中得到了强调。小脑浦肯野神经元和用作电压钳波形的丘脑皮质中继神经元中发生的放电活动表明，α（1G）通道和蚂蚁通道（在较小程度上）产生大的瞬时电流，而与通道相关的电流表现出促进作用，并产生与去极化后电位间隔相关的持续钙进入。通过对网状和中继丘脑神经元活动的模拟，我们发现 α(1I) 电流有助于持续的电活动，而 α1 和 α(1H) 电流则产生短脉冲放电。 NEURON 模型的建模实验进一步表明，α(1G) 通道和 α(1I) 通道参数分别最能解释丘脑皮质中继神经元和网状神经元中描述的 T 通道活动。总而言之，这些数据为 α(1I) 通道在起搏器活动中的作用提供了证据，并进一步证明每个 T 通道成孔亚基都显示出特定的门控特性，这解释了其对神经元放电的独特贡献。
In several types of neurons, firing is an intrinsic property produced by specific classes of ion channels. Low-voltage-activated T-type calcium channels (T-channels), which activate with small membrane depolarizations, can generate burst firing and pacemaker activity. Here we have investigated the specific contribution to neuronal excitability of cloned human T-channel subunits. Using HEK-293 cells transiently transfected with the human alpha(1G) (Cav3.1), alpha(1H) (Cav3.2) and all (Cav3.3) subunits, we describe significant differences among these isotypes in their biophysical properties, which are highlighted in action potential clamp studies. Firing activities occurring in cerebellar Purkinje neurons and in thalamocortical relay neurons used as voltage clamp waveforms revealed that alpha(1G) channels and, to a lesser extent, ant channels produced large and transient currents, while currents related to an channels exhibited facilitation and produced a sustained calcium entry associated with the depolarizing after-potential interval. Using simulations of reticular and relay thalamic neuron activities, we show that alpha(1I) currents contributed to sustained electrical activities, while a, and alpha(1H) currents generated short burst firing. Modelling experiments with the NEURON model further revealed that the alpha(1G) channel and alpha(1I) channel parameters best accounted for T-channel activities described in thalamocortical relay neurons and in reticular neurons, respectively. Altogether, the data provide evidence for a role of alpha(1I) channel in pacemaker activity and further demonstrate that each T-channel pore-forming subunit displays specific gating properties that account for its unique contribution to neuronal firing.