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

通过对大鼠急性解离神经元进行制氨抑素穿孔贴片记录，阐明了Ca^<2+>在中枢神经元中的功能作用。1. Ca^<2+>通过配体门控制离子通道内流：在孤束核（NTS）和Meynert核的神经元中，ATP和kainate被证明可以激活大阳离子电流和随后通过Ca^<2+>直接通过大阳离子通道的Ca^<2+>依赖的K^+电流（I_<K(Ca)>）。随着年龄的增长，NMDA作用下Meynert神经元的大阳离子电流减弱，而kainate作用下Meynert神经元的大阳离子电流增强。NMDA的Ca^<2+>通透性在发育过程中保持不变，而kainate的通透性降低。kainate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（VDCC）内流Ca^<2+>：通过使用特定毒素，VDCC的五种亚型（L，N，P，Q，R）在中枢神经系统不同区域的分布存在差异。生长抑素抑制CA1锥体神经元N型VDCC，而去甲肾上腺素抑制NTS神经元N-、P-和q型VDCC。Meynert“突触钮扣”制备中负责突触传递的VDCC为L型和p型，其中L型与体细胞型表现出不同的特性。3. 细胞内Ca^<2+>库释放Ca^<2+>：代谢性谷氨酸受体、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+>库释放* I_<K(Ca)>激活CA1锥体神经元中的I_<K(Ca)>。这些结果表明Ca^<2+>通过激活I_<K(Ca)>起到负反馈机制的作用，并且该机制在老年大鼠中发育良好。进一步表明，中枢神经系统中的vdcs具有区域和亚型特异性。

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.