Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
Int J Mol Sci. 2018 Mar 11;19(3):808. doi: 10.3390/ijms19030808.
Adenosine triphosphate (ATP) has been well established as an important extracellular ligand of autocrine signaling, intercellular communication, and neurotransmission with numerous physiological and pathophysiological roles. In addition to the classical exocytosis, non-vesicular mechanisms of cellular ATP release have been demonstrated in many cell types. Although large and negatively charged ATP molecules cannot diffuse across the lipid bilayer of the plasma membrane, conductive ATP release from the cytosol into the extracellular space is possible through ATP-permeable channels. Such channels must possess two minimum qualifications for ATP permeation: anion permeability and a large ion-conducting pore. Currently, five groups of channels are acknowledged as ATP-release channels: connexin hemichannels, pannexin 1, calcium homeostasis modulator 1 (CALHM1), volume-regulated anion channels (VRACs, also known as volume-sensitive outwardly rectifying (VSOR) anion channels), and maxi-anion channels (MACs). Recently, major breakthroughs have been made in the field by molecular identification of CALHM1 as the action potential-dependent ATP-release channel in taste bud cells, LRRC8s as components of VRACs, and SLCO2A1 as a core subunit of MACs. Here, the function and physiological roles of these five groups of ATP-release channels are summarized, along with a discussion on the future implications of understanding these channels.
三磷酸腺苷（ATP）已被充分证实为自分泌信号、细胞间通讯和神经递质的重要细胞外配体，具有许多生理和病理生理作用。除了经典的胞吐作用外，许多细胞类型中已经证明了细胞内 ATP 释放的非囊泡机制。尽管带负电荷的大 ATP 分子不能穿过质膜的脂质双层，但通过 ATP 可渗透通道，细胞质中的 ATP 可以进入细胞外间隙进行传导释放。这些通道要具有 ATP 通透的两个最低要求：阴离子通透性和大离子导孔。目前，有五组通道被认为是 ATP 释放通道：连接蛋白半通道、pannexin1、钙稳态调节剂 1（CALHM1）、体积调节阴离子通道（VRACs，也称为容积敏感性外向整流（VSOR）阴离子通道）和 maxi 阴离子通道（MACs）。最近，在味觉细胞中鉴定出钙稳态调节剂 1 是动作电位依赖性 ATP 释放通道、LRRC8 是 VRAC 的组成部分、SLCO2A1 是 MAC 的核心亚基，这些发现为该领域带来了重大突破。本文总结了这五组 ATP 释放通道的功能和生理作用，并讨论了理解这些通道的未来意义。
