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

Ca ^ 2 和CNS神经元中的信号转导。

基本信息

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

项目摘要

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.

使用应用于大鼠急性分离神经元的制霉菌素穿孔贴片记录配置，阐明了Ca 2+ 在中枢神经元中的功能作用。 1. Ca^<2+> 通过配体门控离子通道流入：在孤束核 (NTS) 和 Meynert 核的神经元中，ATP 和红藻氨酸被证明可以激活大的阳离子电流，随后产生 Ca^<2+ > 依赖的 K^+ 电流 (I_<K(Ca)>) 通过 Ca^<2+> 直接通过大阳离子通道。 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弱，而对红藻氨酸的响应则增强。 NMDA的Ca 2+ 渗透性在发育过程中保持恒定，而红藻氨酸的Ca 2+ 渗透性降低。红藻氨酸诱导的 I_<K(Ca)> 在老年大鼠中更为明显。 2. Ca^<2+> 通过电压依赖性 Ca^<2+> 通道 (VDCC) 的流入：通过使用特定毒素，VDCC 的五种亚型（L、N、P、Q、R）被显示为生长抑素在CA1锥体神经元中抑制N型VDCC，而去甲肾上腺素在NTS神经元中抑制N型、P型和Q型。 Meynert“突触按钮”制剂中负责突触传递的 VDCC 为 L 型和 P 型，其中 L 型表现出与体细胞型不同的特性。 3. 细胞内Ca^<2+>储存释放Ca^<2+>：代谢型谷氨酸受体、毒蕈碱乙酰胆碱受体和促甲状腺激素释放激素受体的激动剂通过途径激活CA1锥体神经元中的I_<K(Ca)> G 蛋白 * 磷脂酶 C * IP_3 * 从 IP_3 敏感的 Ca^<2+> 储存中释放 Ca^<2+> * I_<K(Ca)>。这些结果表明Ca^2+通过激活I_<K(Ca)>作为负反馈机制，并且该机制在老年大鼠中得到很好的发展。进一步表明 CNS 中的 VDCC 表现出区域和亚型特定的属性。