Ca^<2+> and signal transduction in CNS neurones.

Ca ^ 2 和CNS神经元中的信号转导。

• 批准号: 04044029
• 负责人: AKAIKE Norio
• 金额: $ 13.76万
• 依托单位: KYUSHU UNIVERSITY (1993-1994)Tohoku University (1992)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for international Scientific Research
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-04044029/
• 关键词: Central neurones; Pharmacological classification; GTP-binding protein; Patch-clamp technique; Nystatin; Calcium channel; Intracellular calcium; Second messenger

The functional roles of Ca^<2+> in central neurones were clarified, using nystatin-perforated patch-recording configuration applied to acutely dissociated neurones of the rats. 1. Influx of Ca^<2+> through Iigand-gated ion channels : In the neurons of the nucleus tractus solitarii (NTS) and Meynert nucleus, ATP and kainate were shown to activate large cationic current and the subsequent Ca^<2+>-dependent K^+ current (I_<K(Ca)>) by way of Ca^<2+> that directly came though the large cation channel. The large cationic current of the Meynert neurones in response to NMDA was diminished as the age of the animals increased, whereas that to kainate was potentiated. Ca^<2+> permeability of NMDA was constant during development, while that of kainate was decreased. Kainate-induced I_<K(Ca)> was more pronounced in the aged rats. 2. Influx of Ca^<2+> through voltage-dependent Ca^<2+> channels (VDCCs) : By using specific toxins, the five subtypes of VDCC (L,N,P,Q,R) were shown to be distributed differentially in different regions of the CNS.Somatostatin suppressed N-type VDCC in CA1 pyramidal neurones, whereas noradrenaline suppressed N-, P- and Q-types in NTS neurones. The VDCC responsible for synaptic transmission in Meynert 'synaptic bouton' preparation was L- and P-types, with the L-type showing different properties to those of somatic one. 3. Release of Ca^<2+> from intracellular Ca^<2+> store : The agonists of metabotropic glutamate receptors, muscarinic acetylcholine receptors and thyrotropin-releasing hormone receptor activated I_<K(Ca)> in CA1 pyramidal neurones by way of G protein * phospholipase C * IP_3 * Ca^<2+> release from IP_3-sensitive Ca^<2+> store * I_<K(Ca)>. These results indicate that Ca^<2+> serves as a negative feedback mechanism by activating I_<K(Ca)> and that the mechanism is well developed in aged rats. It is further suggested that VDCCs in CNS manifest region- and subtype-specific properties.

应用制霉菌素穿孔膜片记录技术对大鼠急性分离的神经元进行记录，阐明了Ca^<2+>在中枢神经元中的功能作用。1.配体门控离子通道Ca^<2+>内流：在孤束核（NTS）和Meynert核神经元中，ATP和红藻氨酸通过直接进入大阳离子通道的Ca^<2 +>激活大阳离子电流和随后的Ca^<2+依赖性K^+电流（I_K（Ca）>）。Meynert神经元响应NMDA的大阳离子电流随着动物年龄的增加而减少，而红藻氨酸则增强。NMDA的Ca^2+渗透性在发育过程中保持不变，而红藻氨酸的Ca^2+渗透性则下降.红藻氨酸诱导的I_（K（Ca））在老年大鼠中更为明显。2.通过电压依赖性Ca^2+通道（VDCCs）的Ca^2+内流：通过使用特定的毒素，VDCCs的五种亚型（L，N，P，Q，R）在中枢神经系统的不同区域有不同的分布，生长抑素抑制CA 1锥体神经元的N型VDCCs，而去甲肾上腺素抑制NTS神经元的N型、P型和Q型VDCCs。Meynert 'synaptic bouton'制备物中负责突触传递的VDCC为L型和P型，其中L型表现出与体细胞型不同的性质。3.胞内Ca^2+库的Ca^2+释放：代谢型谷氨酸受体、毒蕈碱型乙酰胆碱受体和促甲状腺激素释放激素受体激动剂通过G蛋白 * 磷脂酶C * IP_3 * Ca^2+从IP_3敏感的Ca^2+库 * I_K（Ca）>释放激活CA 1锥体神经元的I_K（Ca）。结果表明，Ca^（2+）通过激活I_（K（Ca））而起负反馈作用，这一机制在老年大鼠中已得到充分发展。进一步表明，中枢神经系统中的VDCCs表现出区域和亚型特异性。

项目成果

Akaike,N.: "Effect of KB-2796,a new diphenylpiperazine Ca^<2+> antagonist,on voltage-dependent Ca^<2+> currents and oxidative metabolism in sissociated mammalian CNS neurons." Brain Res.619. 263-270 (1993)

Akaike,N.：“KB-2796（一种新型二苯基哌嗪 Ca^<2> 拮抗剂）对相关哺乳动物 CNS 神经元中电压依赖性 Ca^<2> 电流和氧化代谢的影响。”

Uneyama,J.: "Caffeine and related compounds block inhibitory amino acid-gated Cl^- current in freshly dissociated rat hippocampal neurones." Br.J.Pharmacol.109. 459-465 (1993)

Uneyama, J.：“咖啡因和相关化合物可阻断新鲜分离的大鼠海马神经元中的抑制性氨基酸门控 Cl^-电流。”

Klee, M.R.: Urban & Schwarzenberg. Epilepsy and inhibition, 93-106 (1992)

克利，M.R.：城市

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Agopyan N：“蛋白激酶 A 介导的磷酸化仅减少急性分离的腹内侧下丘脑神经元中的快速脱敏甘氨酸电流。”

Nabekura, J.: "Developmental change in voltage dependency of NMDA receptor-mediated response in nucleus tractus solitarii neurons." Brain Res.648. 152-156 (1994)

Nabekura, J.：“孤束核神经元中 NMDA 受体介导的反应的电压依赖性的发育变化。”