Function of voltage-dependent Ca^<2+> channels in central nervous system neurons.

中枢神经系统神经元中电压依赖性Ca^2通道的功能。

• 批准号: 09680822
• 负责人: MIYAKAWA Hiroyoshi
• 金额: $ 2.11万
• 依托单位: Tokyo University of Pharmacy and Life Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09680822/
• 关键词: central nervous system neuron; deudrite; voltage-dependent Ca^<2+> channel; Ca^<2+> imaging; 小脳プルキンエ細胞; 電位依存性カルシウムチャネル; 小脳; プルキンエ細胞; Ca^<2+>チャネル; K^+チャネル; Fura-2

The objective of this project was to study spatial distribution of functional voltage-gated Ca^<2+> channels in the dendrites of central nervous system neurons in slice preparations using a Ca^<2+> imaging technique in order to understand the roles of Ca^<2+> channels. Several different types of voltage-gated Ca^<2+> has been shown to be distributed in central nervous system neurons and classified according to their pharmacological and kinetic properties. Those include T, N, L, and P-type of Ca^<2+> channels.It has been reported from the studies using isolated or cultured neurons that cerebellar Purkinje neurons are rich in P-type Ca^<2+> channels, and that low-threshold Ca^<2+> channels are also distributed in Purkinje neurons. We made cerebellar slices from rats and stained individual Purkinje neurons with fluorescent Ca^<2+> indicator dye using whole-cell pipetts. The dendrites of Purkinje neurons were stimulated by depolarizing the cell body in the presence of TTX, a Na^+ channel b … More locker, and the change in intracellular Ca^<2+> level was measured with a cooled CCD camera. Addition of a blocker for P-type channel abolished Ca^<2+> dependent action spikes and accompanying transient Ca^<2+> increase leaving a significant Ca^<2+> rise in the dendrites. Ca^<2+> imaging study showed that this Ca^<2+> rise was due to activation of low-threshold Ca^<2+> channels and that under a condition where voltage-gated K^+ channels were pharmacologically blocked, this Ca^<2+> rise was suppressed by Ni^<2+> , a blocker for low-threshold Ca^<2+> channels. Based on these findings we concluded that low-threshold Ca^<2+> channels and low-threshold K^+ channels are distributed along the dendrites of cerebellar Purkinje neurons. A simulation study to computationally reconstruct Purkinje neurons using a compartmental model suggested that those low-threshold Ca^<2+> and K^+ channels are responsible for the Ca^<2+>-dependent plateau potential.Further studies are needed to understand how these low-threshold ion channels in the dendrites contribute the mechanisms for integrating synaptic inputs in central nervous system neurons. Less

本研究的目的是利用Ca^<2+>成像技术研究功能性电压门控Ca^<2+>通道在中枢神经系统神经元树突中的空间分布，以了解Ca^<2+>通道的作用。几种不同类型的电压门控Ca^<2+>已被证明分布在中枢神经系统神经元中，并根据其药理学和动力学特性进行分类。在分离和培养的小脑浦肯野神经元中发现，小脑浦肯野神经元中含有丰富的P型Ca^<2 +>通道，并且在浦肯野神经元中也存在低阈值Ca^<2+>通道。我们制作了大鼠小脑切片，并使用全细胞移液管用荧光Ca^2+指示染料对单个浦肯野神经元进行染色。在存在TTX（一种Na^+通道B）的情况下，通过去极化细胞体来刺激浦肯野神经元的树突 ...更多信息 用冷却的CCD照相机测量细胞内Ca^<2+>水平的变化。加入P-型通道阻断剂可消除Ca^2+依赖性动作峰和伴随的短暂Ca^2+升高，使树突中的Ca^2+显著升高。Ca^2+成像研究表明，这种Ca^2+升高是由于低阈值Ca^2+通道的激活，在电压门控性K^+通道被阻断的情况下，这种Ca^2+升高被低阈值Ca^2+通道阻断剂Ni^2+抑制。基于这些结果，我们得出结论，低阈值Ca^<2+>通道和低阈值K^+通道沿着小脑浦肯野神经元的树突分布。用房室模型对浦肯野神经元进行计算机重构的模拟研究表明，这些低阈值的Ca^2+和K^+通道是Ca^2+依赖的平台电位的主要来源，但这些低阈值的离子通道在中枢神经系统神经元整合突触输入的机制中的作用还有待于进一步的研究。少

项目成果

Watanabe S.et al.: "Differential roles for two Types of voltage gated Ca^<2+> channds in the dendeites of cerebellar Purkinje neurons" Brain Research. 791. 43-55 (1998)

Watanabe S.et al.：“两种类型的电压门控 Ca^<2> 通道在小脑浦肯野神经元树突中的不同作用”大脑研究。

Watanabe et al.: "Differential roles for two types of voltage gated Ca^<2+> channels in the dendrites of cerebellar Purkinje neurons" Brain Res.791. 43-55 (1998)

Watanabe 等人：“小脑浦肯野神经元树突中两种类型的电压门控 Ca^2 通道的不同作用”Brain Res.791。

Watanabe S. et al.: "Differential roles for two Types of voltage gated Ca^<2+> channds in the dendrites of cerebellar Purkinie ueurons" Brain Research. 791. 43-55 (1998)

Watanabe S. 等人：“小脑 Purkinie 神经元树突中两种电压门控 Ca^2 通道的不同作用”大脑研究。