Action potential broadening in a presynaptic channelopathy.
Action potential broadening in a presynaptic channelopathy.
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DOI：
10.1038/ncomms12102
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发表时间：
2016-07-06
影响因子：
16.6
通讯作者：
Kullmann DM
中科院分区：
文献类型：
--
作者：
Begum R;Bakiri Y;Volynski KE;Kullmann DM
在许多发作性神经通道病中，大脑发育和发作间歇功能没有受到影响，这可能是由于突触传递的稳态可塑性所致。发作性共济失调1型是由钾通道Kv1.1的错义突变引起的，Kv1.1在小脑篮细胞的终末大量表达。小抑制终末的突触前动作电位尚未被描述，也不知道发育可塑性是否补偿了Kv1.1功能障碍的影响。在这里，我们使用视觉目标膜片钳记录来自携带共济失调相关突变的小鼠及其野生型窝种的篮子细胞末端。突触前棘波之后伴随着明显的后除极，并被Kv1.1的药物阻断或显性共济失调相关突变所扩大。体细胞记录无法检测到这样的变化。峰宽导致钙离子内流和GABA释放增加，浦肯野细胞自发放电减少。我们没有发现遗传性Kv1.1功能障碍的发育补偿的证据。发作性共济失调1型是由钾通道Kv1.1突变引起的，Kv1.1存在于小脑篮细胞中。在这里，作者使用电生理学技术来表征这些突变通道，并观察到这些变化导致自发浦肯野细胞放电减少，但没有证据表明发育代偿。
Brain development and interictal function are unaffected in many paroxysmal neurological channelopathies, possibly explained by homoeostatic plasticity of synaptic transmission. Episodic ataxia type 1 is caused by missense mutations of the potassium channel Kv1.1, which is abundantly expressed in the terminals of cerebellar basket cells. Presynaptic action potentials of small inhibitory terminals have not been characterized, and it is not known whether developmental plasticity compensates for the effects of Kv1.1 dysfunction. Here we use visually targeted patch-clamp recordings from basket cell terminals of mice harbouring an ataxia-associated mutation and their wild-type littermates. Presynaptic spikes are followed by a pronounced afterdepolarization, and are broadened by pharmacological blockade of Kv1.1 or by a dominant ataxia-associated mutation. Somatic recordings fail to detect such changes. Spike broadening leads to increased Ca2+ influx and GABA release, and decreased spontaneous Purkinje cell firing. We find no evidence for developmental compensation for inherited Kv1.1 dysfunction. Episodic ataxia type 1 is caused by mutations in the potassium channel Kv1.1, which is found in cerebellar basket cells. Here, the authors use electrophysiology techniques to characterize these mutant channels, and observe that the changes result in decreased spontaneous Purkinje cell firing with no evidence for developmental compensation.