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肾上腺嗜铬细胞中的L型钙通道:在起搏和分泌中的作用。

L-type calcium channels in adrenal chromaffin cells: role in pace-making and secretion.

作者信息

Marcantoni A, Baldelli P, Hernandez-Guijo J M, Comunanza V, Carabelli V, Carbone E

机构信息

Department of Neuroscience, NIS Center of Excellence, CNISM Research Unit, Corso Raffaello 30, 10125 Torino, Italy.

出版信息

Cell Calcium. 2007 Oct-Nov;42(4-5):397-408. doi: 10.1016/j.ceca.2007.04.015. Epub 2007 Jun 11.

Abstract

Voltage-gated L-type (Cav1.2 and Cav1.3) channels are widely expressed in cardiovascular tissues and represent the critical drug-target for the treatment of several cardiovascular diseases. The two isoforms are also abundantly expressed in neuronal and neuroendocrine tissues. In the brain, Cav1.2 and Cav1.3 channels control synaptic plasticity, somatic activity, neuronal differentiation and brain aging. In neuroendocrine cells, they are involved in the genesis of action potential generation, bursting activity and hormone secretion. Recent studies have shown that Cav1.2 and Cav1.3 are also expressed in chromaffin cells but their functional role has not yet been identified despite that L-type channels possess interesting characteristics, which confer them an important role in the control of catecholamine secretion during action potentials stimulation. In intact rat adrenal glands L-type channels are responsible for adrenaline and noradrenaline release following splanchnic nerve stimulation or nicotinic receptor activation. L-type channels can be either up- or down-modulated by membrane autoreceptors following distinct second messenger pathways. L-type channels are tightly coupled to BK channels and activate at relatively low-voltages. In this way they contribute to the action potential hyperpolarization and to the pace-maker current controlling action potential firings. L-type channels are shown also to regulate the fast secretion of the immediate readily releasable pool of vesicles with the same Ca(2+)-efficiency of other voltage-gated Ca(2+) channels. In mouse adrenal slices, repeated action potential-like stimulations drive L-type channels to a state of enhanced stimulus-secretion efficiency regulated by beta-adrenergic receptors. Here we will review all these novel findings and discuss the possible implication for a specific role of L-type channels in the control of chromaffin cells activity.

摘要

电压门控L型(Cav1.2和Cav1.3)通道广泛表达于心血管组织,是治疗多种心血管疾病的关键药物靶点。这两种亚型在神经元和神经内分泌组织中也大量表达。在大脑中,Cav1.2和Cav1.3通道控制突触可塑性、体细胞活动、神经元分化和大脑衰老。在神经内分泌细胞中,它们参与动作电位的产生、爆发活动和激素分泌。最近的研究表明,Cav1.2和Cav1.3也表达于嗜铬细胞,但尽管L型通道具有有趣的特性,使其在动作电位刺激期间儿茶酚胺分泌的控制中发挥重要作用,但其功能作用尚未确定。在完整的大鼠肾上腺中,L型通道负责在内脏神经刺激或烟碱样受体激活后肾上腺素和去甲肾上腺素的释放。L型通道可通过不同的第二信使途径被膜自身受体上调或下调。L型通道与BK通道紧密偶联,并在相对低电压下激活。通过这种方式,它们有助于动作电位超极化和控制动作电位发放的起搏电流。L型通道还显示出以与其他电压门控Ca(2+)通道相同的Ca(2+)效率调节快速可释放囊泡池的快速分泌。在小鼠肾上腺切片中,重复的动作电位样刺激使L型通道进入由β-肾上腺素能受体调节的增强刺激-分泌效率状态。在此,我们将综述所有这些新发现,并讨论L型通道在控制嗜铬细胞活性中的特定作用的可能意义。

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