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BK通道β4亚基降低齿状回兴奋性并预防颞叶癫痫。

BK channel beta4 subunit reduces dentate gyrus excitability and protects against temporal lobe seizures.

作者信息

Brenner Robert, Chen Qing H, Vilaythong Alex, Toney Glenn M, Noebels Jeffrey L, Aldrich Richard W

机构信息

Department of Physiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78229, USA.

出版信息

Nat Neurosci. 2005 Dec;8(12):1752-9. doi: 10.1038/nn1573. Epub 2005 Oct 30.

Abstract

Synaptic inhibition within the hippocampus dentate gyrus serves a 'low-pass filtering' function that protects against hyperexcitability that leads to temporal lobe seizures. Here we demonstrate that calcium-activated potassium (BK) channel accessory beta4 subunits serve as key regulators of intrinsic firing properties that contribute to the low-pass filtering function of dentate granule cells. Notably, a critical beta4 subunit function is to preclude BK channels from contributing to membrane repolarization and thereby broaden action potentials. Longer-duration action potentials secondarily recruit SK channels, leading to greater spike frequency adaptation and reduced firing rates. In contrast, granule cells from beta4 knockout mice show a gain-of-function for BK channels that sharpens action potentials and supports higher firing rates. Consistent with breakdown of the dentate filter, beta4 knockouts show distinctive seizures emanating from the temporal cortex, demonstrating a unique nonsynaptic mechanism for gate control of hippocampal synchronization leading to temporal lobe epilepsy.

摘要

海马齿状回内的突触抑制发挥着“低通滤波”功能,可防止导致颞叶癫痫的过度兴奋。我们在此证明,钙激活钾(BK)通道辅助β4亚基作为内在放电特性的关键调节因子,有助于齿状颗粒细胞的低通滤波功能。值得注意的是,β4亚基的一个关键功能是阻止BK通道参与膜复极化,从而拓宽动作电位。持续时间更长的动作电位继而募集小电导钙激活钾(SK)通道,导致更大的放电频率适应性和降低的放电率。相比之下,β4基因敲除小鼠的颗粒细胞显示BK通道功能增强,使动作电位变尖锐并支持更高的放电率。与齿状滤波器功能破坏一致,β4基因敲除小鼠表现出源自颞叶皮质的独特癫痫发作,证明了一种导致颞叶癫痫的海马同步门控独特非突触机制。

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