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离子通道对血小板和巨核细胞功能的独特贡献。

The unique contribution of ion channels to platelet and megakaryocyte function.

机构信息

Department of Cell Physiology & Pharmacology, University of Leicester, Leicester, UK.

出版信息

J Thromb Haemost. 2012 Sep;10(9):1722-32. doi: 10.1111/j.1538-7836.2012.04837.x.

DOI:10.1111/j.1538-7836.2012.04837.x
PMID:22741535
Abstract

Ion channels are transmembrane proteins that play ubiquitous roles in cellular homeostasis and activation. In addition to their recognized role in the regulation of ionic permeability and thus membrane potential, some channel proteins possess intrinsic kinase activity, directly interact with integrins or are permeable to molecules up to ≈1000 Da. The small size and anuclear nature of the platelet has often hindered progress in understanding the role of specific ion channels in hemostasis, thrombosis and other platelet-dependent events. However, with the aid of transgenic mice and 'surrogate' patch clamp recordings from primary megakaryocytes, important unique contributions to platelet function have been identified for several classes of ion channel. Examples include ATP-gated P2X1 channels, Orai1 store-operated Ca2+ channels, voltage-gated Kv1.3 channels, AMPA and kainate glutamate receptors and connexin gap junction channels. Furthermore, evidence exists that some ion channels, such as NMDA glutamate receptors, contribute to megakaryocyte development. This review examines the evidence for expression of a range of ion channels in the platelet and its progenitor cell, and highlights the distinct roles that these proteins may play in health and disease.

摘要

离子通道是跨膜蛋白,在细胞内稳态和激活中发挥普遍作用。除了其在调节离子通透性和膜电位方面的公认作用外,一些通道蛋白还具有内在的激酶活性,直接与整合素相互作用,或者对高达约 1000 Da 的分子具有通透性。血小板的小尺寸和无核性质常常阻碍了对特定离子通道在止血、血栓形成和其他依赖血小板的事件中的作用的理解。然而,借助转基因小鼠和来自原代巨核细胞的“替代”膜片钳记录,已经确定了几类离子通道对血小板功能的重要独特贡献。例如,ATP 门控 P2X1 通道、Orai1 储存操纵的 Ca2+ 通道、电压门控 Kv1.3 通道、AMPA 和 kainate 谷氨酸受体和缝隙连接通道。此外,有证据表明,一些离子通道,如 NMDA 谷氨酸受体,有助于巨核细胞的发育。这篇综述检查了一系列离子通道在血小板及其祖细胞中的表达证据,并强调了这些蛋白质在健康和疾病中可能发挥的不同作用。

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