L-type calcium channels in adrenal chromaffin cells: Role in pace-making and secretion
L-type calcium channels in adrenal chromaffin cells: Role in pace-making and secretion
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DOI：
10.1016/j.ceca.2007.04.015
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发表时间：
2007-10-01
期刊：
影响因子：
4
通讯作者：
Carbone, E.
中科院分区：
文献类型：
--
作者：
Marcantoni, A.;Baldelli, P.;Carbone, E.
电压门控l型（Cav 1.2和Cav 1.3）通道在心血管组织中广泛表达，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，Cav 1.2和Cav 1.3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，它们参与动作电位产生、爆发活动和激素分泌的发生。最近的研究表明，Cav 1.2和Cav 1.3也在染色质细胞中表达，但其功能作用尚未确定，尽管l型通道具有有趣的特性，这些特性赋予它们在动作电位刺激时控制儿茶酚胺分泌的重要作用。在完整的大鼠肾上腺中，l型通道负责在内脏神经刺激或尼古丁受体激活后肾上腺素和去甲肾上腺素的释放。l型通道可被膜自受体沿不同的第二信使通路向上或向下调节。l型通道与BK通道紧密耦合，在相对较低的电压下激活。通过这种方式，它们有助于动作电位的超极化和控制动作电位放电的起搏器电流。l型通道也被证明可以调节囊泡的快速分泌，具有与其他电压门控Ca2+通道相同的Ca2+效率。在小鼠肾上腺切片中，重复动作电位样刺激将l型通道驱动到由β肾上腺素能受体调节的刺激分泌效率增强的状态。在这里，我们将回顾所有这些新发现，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含义。(c) 2007 Elsevier Ltd.版权所有。
Voltage-gated L-type (Cav 1.2 and Cav 1.3) 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, Cav 1.2 and Cav 1.3 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 Cav 1.2 and Cav 1.3 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 Ca2+-efficiency of other voltage-gated Ca2+ 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. (c) 2007 Elsevier Ltd. All rights reserved.