Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5) , Jülich, Germany.
University of Cologne, Faculty of Medicine and University Hospital Cologne, Institute of Radiochemistry and Experimental Molecular Imaging , Cologne, Germany.
Channels (Austin). 2020 Dec;14(1):362-379. doi: 10.1080/19336950.2020.1829842.
Voltage-gated calcium channels (VGCCs) are critical for Ca influx into all types of excitable cells, but their exact function is still poorly understood. Recent reconstruction of homology models for all human VGCCs at atomic resolution provides the opportunity for a structure-based discussion of VGCC function and novel insights into the mechanisms underlying Ca selective flux through these channels. In the present review, we use these data as a basis to examine the structure, function, and Zn-induced modulation of Ca2.3 VGCCs, which mediate native R-type currents and belong to the most enigmatic members of the family. Their unique sensitivity to Zn and the existence of multiple mechanisms of Zn action strongly argue for a role of these channels in the modulatory action of endogenous loosely bound Zn, pools of which have been detected in a number of neuronal, endocrine, and reproductive tissues. Following a description of the different mechanisms by which Zn has been shown or is thought to alter the function of these channels, we discuss their potential (patho)physiological relevance, taking into account what is known about the magnitude and function of extracellular Zn signals in different tissues. While still far from complete, the picture that emerges is one where Ca2.3 channel expression parallels the occurrence of loosely bound Zn pools in different tissues and where these channels may serve to translate physiological Zn signals into changes of electrical activity and/or intracellular Ca levels.
电压门控钙通道（VGCCs）对于所有类型的可兴奋细胞中的 Ca 内流至关重要，但它们的确切功能仍知之甚少。最近，对所有人类 VGCC 进行同源建模的原子分辨率重建，为基于结构的 VGCC 功能讨论以及这些通道中 Ca 选择性通量的机制提供了新的见解。在本综述中，我们使用这些数据作为基础，来研究 Ca2.3 VGCC 的结构、功能和 Zn 诱导的调制，Ca2.3 VGCC 介导天然 R 型电流，是家族中最神秘的成员之一。它们对 Zn 的独特敏感性以及 Zn 作用的多种机制的存在强烈表明这些通道在内源性松散结合 Zn 的调节作用中发挥作用，在许多神经元、内分泌和生殖组织中已经检测到了这种 Zn 池。在描述了 Zn 已经显示或被认为改变这些通道功能的不同机制之后，我们讨论了它们的潜在（病理）生理学相关性，同时考虑到已知的不同组织中外源 Zn 信号的幅度和功能。尽管还远未完成，但出现的情况是，Ca2.3 通道的表达与不同组织中松散结合的 Zn 池的发生平行，并且这些通道可能有助于将生理 Zn 信号转化为电活动和/或细胞内 Ca 水平的变化。
