Department of Pediatrics, University of California-Irvine, Irvine, CA 92697-4475, USA.
Curr Opin Neurobiol. 2011 Dec;21(6):873-9. doi: 10.1016/j.conb.2011.06.013. Epub 2011 Jul 23.
Epilepsy is the third most common brain disorder and affects millions of people. Epilepsy is characterized by the occurrence of spontaneous seizures, that is, bursts of synchronous firing of large populations of neurons. These are believed to result from abnormal regulation of neuronal excitability that favors hypersynchrony. Among the intrinsic conductances that govern neuronal excitability, the hyperpolarization-activated current (I(h)) plays complex and important roles in the fine-tuning of both cellular and network activity. Not surprisingly, dysregulation of I(h) and/or of its conducting ion-channels (HCN) has been strongly implicated in various experimental models of epilepsy, as well as in human epilepsy. Here we provide an overview of recent findings on the distinct physiological roles played by I(h) in specific contexts, and the cellular mechanisms that underlie these functions, including the subunit make-up of the channels. We further discuss current knowledge of dysregulation of I(h) and HCN channels in epilepsy in light of the multifaceted functions of I(h) in the brain.
癫痫是第三大脑部疾病，影响着数百万人。癫痫的特征是自发性癫痫发作，即神经元大群体的同步放电爆发。据信，这些是由于神经元兴奋性的异常调节导致过度同步化所致。在调节神经元兴奋性的内在电导中，超极化激活电流（I(h)）在细胞和网络活动的精细调节中起着复杂而重要的作用。毫不奇怪，I(h)及其传导离子通道（HCN）的失调已在各种实验性癫痫模型以及人类癫痫中得到了强烈的暗示。在这里，我们概述了 I(h)在特定情况下发挥的不同生理作用的最新发现，以及这些功能的细胞机制，包括通道的亚基组成。我们还根据 I(h)在大脑中的多方面功能，讨论了癫痫中 I(h)和 HCN 通道失调的现有知识。
