Age-dependent modulation of hippocampal excitability by KCNQ-channels
Age-dependent modulation of hippocampal excitability by KCNQ-channels
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DOI：
10.1016/s0920-1211(02)00249-8
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发表时间：
2003-02-01
影响因子：
2.2
通讯作者：
Kaneko, S
中科院分区：
文献类型：
--
作者：
Okada, M;Zhu, G;Kaneko, S
最近，KCNQ相关K+通道（KCNQ通道）家族成员KCNQ 2或KCNQ 3的突变被确定为良性家族性新生儿惊厥（BFNC）的原因。然而，BFNC的年龄依赖性发展和自发缓解的确切致病机制仍有待阐明。为了阐明BFNC的年龄依赖性病因，我们确定了大鼠海马中KCNQ通道、GABA能和神经递质传递的年龄依赖性功能转换。采用64通道多电极盘（MED 64）、全细胞记录、体外释放技术和在体微透析生物传感器技术，观察了KCNQ通道、GABA和谷氨酸受体抑制剂对大鼠海马神经元兴奋性传播和神经递质释放的影响。抑制KCNQ-通道增强去极化诱导的谷氨酸和GABA的释放在P0-P7，但不是在P14-P28。KCNQ通道的抑制放大了从PO到P14的神经元兴奋性传播：在P3达到最大，但这种效应在P28消失。GABA（A）受体抑制令人惊讶地减少了P0-P3期间的神经元兴奋性传播，但在P7没有。AMPA/谷氨酸受体抑制减少了整个研究期间神经元兴奋性的传播。KCNQ通道抑制缩短了尖峰频率适应，但这种刺激在P14期间更占主导地位< 7 than P >。在生命的第一周，KCNQ通道作为一个主要的抑制系统，而在此期间之后，GABA能传递从兴奋性功能切换到抑制性功能。相反，介电传递是从PO获得的兴奋功能。这些发现表明，年龄依赖性发展和自发缓解的BFNC的致病机制，至少部分地与年龄依赖性的抑制性KCNQ通道活性的降低和年龄依赖性的GABA能系统的功能转换之间的相互作用，从兴奋性到抑制性作用在新生儿CNS。(C)2002 Elsevier Science B. V.保留所有权利。
Recently, mutations of KCNQ2 or KCNQ3, members of the KCNQ-related K+-channel (KCNQ-channel) family, were identified as cause of benign familial neonatal convulsions (BFNC). However, the exact pathogenic mechanisms of age-dependent development and spontaneous remission of BFNC remain to be elucidated. To clarify the age-dependent etiology of BFNC, we determined age-dependent functional switching of KCNQ-channels, GABAergic- and glutamatergic-transmission in rat hippocampus. The effects of inhibitors of KCNQ-channel, GABA- and glutamate-receptors on propagation of neuronal-excitability and neurotransmitter release were determined by 64-channel multielectrode-dish (MED64), whole-cell recording, in vitro release technique and in vivo microdialysis biosensor, using rat hippocampus from day of birth (PO) to postnatal-day 56 (P56). Inhibition of KCNQ-channels enhanced depolarization-induced glutamate and GABA releases during P0-P7, but not during P14-P28. Inhibition of KCNQ-channels magnified neuronal-excitability propagation from PO to P14: maximal at P3, but this effect disappeared by P28. GABA(A)-receptor inhibition surprisingly reduced neuronal-excitability propagation during P0-P3, but not at P7. AMPA/glutamate-receptors inhibition reduced propagation of neuronal-excitability throughout the study period. KCNQ-channels inhibition shortened spike-frequency adaptation, but this stimulation was more predominant during P < 7 than P > 14. During the first week of life, KCNQ-channels performed as a predominant inhibitory system, whereas after this period GABAergic-transmission switched from excitatory to inhibitory function. Contrary, glutamatergic-transmission has acquired as excitatory function from PO. These findings suggest that the pathogenic mechanisms of age-dependent development and spontaneous remission of BFNC are, at least partially, associated with the interaction between age-dependent reduction of inhibitory KCNQ-channel activity and age-dependent functional switching of the GABAergic- system from excitatory to inhibitory action in neonatal CNS. (C) 2002 Elsevier Science B.V. All rights reserved.