期刊
HIPPOCAMPUS
卷 20, 期 7, 页码 877-887出版社
WILEY-LISS
DOI: 10.1002/hipo.20694
关键词
epileptogenesis; fast ripples; synchronicity; dendritic potentials; transient A-type potassium current; Kv4.2
资金
- Swedish VR [621-2007-4223]
- NIH [MH061492-06A2]
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH061492] Funding Source: NIH RePORTER
A range of ionic currents have been suggested to be involved in distinct aspects of epileptogenesis. Based on pharmacological and genetic studies, potassium currents have been implicated, in particular the transient A-type potassium current (K(A)). Epileptogenic activity comprises a rich repertoire of characteristics, one of which is synchronized activity of principal cells as revealed by occurrences of for instance fast ripples. Synchronized activity of this kind is particularly efficient in driving target cells into spiking. In the recipient cell, this synchronized input generates large brief compound excitatory postsynaptic potentials (EPSPs). The fast activation and inactivation of K(A) lead us to hypothesize a potential role in suppression of such EPSPs. In this work, using computational modeling, we have studied the activation of K(A) by synaptic inputs of different levels of synchronicity. We find that K(A) participates particularly in suppressing inputs of high synchronicity. We also show that the selective suppression stems from the current's ability to become activated by potentials with high slopes. We further show that K(A) suppresses input mimicking the activity of a fast ripple. Finally, we show that the degree of selectivity of K(A) can be modified by changes to its kinetic parameters, changes of the type that are produced by the modulatory action of KChIPs and DPPs. We suggest that the wealth of modulators affecting K(A) might be explained by a need to control cellular excitability in general and suppression of responses to synchronicity in particular. We also suggest that compounds changing K(A)-kinetics may be used to pharmacologically improve epileptic status. (C) 2009 Wiley-Liss, Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据