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Title: 大鼠可兴奋性细胞上的离子通道与钙离子调控
Author: 于晓
Degree Level: 博士
Issued Date: 2004
Degree Grantor: 中国科学院神经科学研究所
Place of Degree Grantor: 中国科学院神经科学研究所
Supervisor: 周专
Keyword: 内质网钙库 ; 起搏离子通道 ; 钙离子 ; 胰腺β细胞 ; 背根神经节神经元 ; 心室肌
Abstract: 作为最重要的第二信使,钙离子控制许多生理过程,例如,细胞分泌和肌肉收缩。静息状态下胞浆中钙离子水平很低,而细胞受到某些刺激后,钙离子可通过胞膜上的钙通透性通道或胞内钙离子库的钙释放通道提高胞浆中钙离子浓度,进而引起各种生理活动。在胰腺p细胞上,人们已知葡萄糖刺激能够使细胞去极化,然后钙离子通过胞膜上电压依赖的钙通道进入胞内,最终导致胰岛素的分泌,是典型的“刺激一分泌祸联”途径。在神经元和心肌细胞中,通过电压依赖的钙通道内流的钙离子是动作电位诱导的神经递质释放和心肌收缩的关键。为了更全面地了解大鼠可兴奋性细胞上的钙离子依赖的生理活动,我们研究了大鼠胰腺β细胞内的钙离子库,以及背根神经节神经元和心室肌细胞中起搏离子通道的钙通透性。1)我们对胰腺p细胞胞内钙库的研究发现,其ER钙库在功能上是不连续的,可以分为只含IP3受体的钙库和Ryanodine与IP3受体共存的钙库,并发现硫喷妥钠可以引起胞内IP3敏感的钙库释放钙离子,从而引起细胞分泌。2)我们发现构建的两种HCN通道以及背根神经节神经元上的起搏离子通道能够通透钙离子,其钙离子分电流为0.47%-0.60%,而且激活背根神经节神经元上的起搏离子通道能够易化动作电位引起的细胞分泌。3)在大鼠心室肌上超极化刺激激活的起搏离子通道,也能够通透钙离子,从而引起心肌细胞收缩和动作电位形状的改变。综上所述,通过一些非经典途径提高胞内钙离子水平也能引起一定的生理活动,它们可能在正常条件下参与细胞分泌或心脏起搏活动的调节,也可能在病理条件下有相对重要的作用。
English Abstract: As the most important second messenger, Ca2+ controls many physiological events, such as neurotransmitter release and muscle contraction. While cytoplastic Ca2+ concentration is usually kept below 0.1-0.2 jaM, it will rise to function in intracellular signaling after excitation, with Ca2+ passing through Ca2+-permeable ion channels in plasma membrane and Ca2+-release channels in endoplasmic reticulum/sarcoplasmic reticulum (ER/SR). In pancreatic p cells, Ca2+ couples excitation (high glucose) and insulin secretion, through voltage-dependent Ca2+ channels (VDCCs). In neurons and cardiac myocytes, when action potentials depolarize the plasma membrane, Ca2+ influx through VDCCs is a key point in transmitter release and muscle contraction. In order to widely understand Ca2+-dependent physiological events, we studied Ca~+ stores in rat pancreatic P cells, and pacemaker channels in rat DRG neurons and rat ventricular myocytes. The main results obtained are listed below: We found ER Ca2+ store is functionally separate in pancreatic p cells, which may be divided into IP3 and Ryanodine common Ca2T store, and only IP3-sensitive store. Thiopentone can induce insulin secretion due to IP3-sensitive calcium release. Using combined whole-cell recording and fluorescence Ca2+ imaging, we found Ca2+ can permeate hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, and contribute 0.47%-0.60% of total HCN4 and HCN2 induced currents, respectively. In DRG neurons, Ih channel is also permeable to Ca~+, which contributes to activity-evoked neuronal secretion. 3) In rat ventricular myocyte, we found Ca2+, when entering the cell through If channels, can induce muscle contraction at negative membrane potentials and shorten the action potential duration. Taken together, our results demonstrated that Ca2+ rise by non-classical pathway also plays some important roles in physiological events. This is important for modulation of cell secretion and muscle contraction under nonnal conditions, and may represent a previously undiscovered mechanism in certain pathophysiological conditions.
Language: 中文
Content Type: 学位论文
URI: http://ir.sibs.ac.cn/handle/331001/2260
Appears in Collections:神经所(总)_学位论文

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Recommended Citation:
大鼠可兴奋性细胞上的离子通道与钙离子调控.于晓[d].中国科学院神经科学研究所,2004.20-25
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