A novel role for HERG K+ channels: Spike-frequency adaptation
A novel role for HERG K+ channels: Spike-frequency adaptation
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DOI：
10.1111/j.1469-7793.1997.313bn.x
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发表时间：
1997-06-01
影响因子：
5.5
通讯作者：
Wanke, E
中科院分区：
文献类型：
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作者：
Chiesa, N;Rosati, B;Wanke, E
1.具有快速Na+和延迟K+通道的Hodgkin-Huxley神经元的规则放电可以通过附加HERG（人类eag相关基因）通道转换为适应性放电。2．通过研究长期暴露于视黄酸诱导分化的 F-11 DRG 神经元 x 神经母细胞瘤杂交细胞的放电特性，验证了计算机模型的预测。这些表达 HERG 电流 (I-HERG) 的细胞，当电流被长时间去极化钳制时，其放电表现出明显的尖峰频率适应。3．与预测相一致的是，Ⅲ类抗心律失常药物对I-HERG的选择性阻断往往导致尖峰频率适应消失，由适应放电向规律放电转变。4．据提议，除了在心脏动作电位复极化中的作用外，HERG 通道还可以维持尖峰频率适应过程，因此有助于以类似于 K+ 电流、I-AHP、I-C 和 I-M 的方式控制突发持续时间。除了已知的心律失常综合征 (LQT2) 之外，基因突变或 HERG 表达改变还可能导致神经或内分泌细胞无法适应重复刺激而持续的过度兴奋状态。这可能有助于阐明尚未明确的特发性家族性癫痫的发病机制。
1. The regular firing of a Hodgkin-Huxley neurone endowed with fast Na+ and delayed K+ channels can be converted into adapting firing by appending HERG (human eag-related gene) channels.2. The computer model predictions were verified by studying the firing properties of F-11 DRG neurone x neuroblastoma hybrid cells induced to differentiate by long-term exposure to retinoic acid. These cells, which express HERG currents (I-HERG), show clear spike-frequency adaptation of their firing when current clamped with long depolarizations.3. In agreement with the prediction, the selective blocking of I-HERG by class III antiarrhythmic drugs always led to the disappearance of the spike-frequency adaptation, and the conversion of adapting firing to regular firing.4. It is proposed that, in addition to their role in the repolarization of the heart action potential, HERG channels may sustain a process of spike-frequency adaptation, and hence contribute to the control of burst duration in a way that is similar to that of the K+ currents, I-AHP, I-C and I-M. In addition to the known cardiac arrhythmia syndrome (LQT2), genetic mutations or an altered HERG expression could lead to continous hyperexcitable states sustained by the inability of nerve or endocrine cells to accommodate to repetitive stimuli. This might help in clarifying the pathogenesis of still undefined idiopathic familial epilepsies.