Permeation through store-operated CRAC channels in divalent-free solution: potential problems and implications for putative CRAC channelgenes
Permeation through store-operated CRAC channels in divalent-free solution: potential problems and implications for putative CRAC channelgenes
复制标题
DOI：
10.1016/s0143416002001914
复制
发表时间：
2002-11-01
期刊：
影响因子：
4
通讯作者：
Parekh, AB
中科院分区：
文献类型：
--
作者：
Bakowski, D;Parekh, AB
CREC通道在生理和病理状态下都是重要的钙通道。了解这些通道是如何控制的是重要的，因为这不仅将提供对连接细胞内存储和质膜通道的新的信号转导途径的洞察，而且可能具有临床意义。确定CRAC通道的分子同一性肯定是向前迈出的一大步。像所有的钙离子选择性通道一样，CRAC通道在无二价的外部溶液中失去了对大的单价Na+电流的选择性。这种方法提供了对通道渗透性和选择性的新见解，并识别了CRAC通道和电压额定钙通道(VOCC)之间的一些有趣的差异。然而，对无二价溶液的研究是一把双刃剑。电生理学家需要警惕，因为在无二价的外部溶液中用于研究/(CRAC)的一些条件，特别是从记录吸管溶液中省略镁离子/镁-三磷酸腺苷，激活了通过镁核苷酸调节的金属离子电流(Magnum；TRPM7)通道的额外电流。这个通道是过去被归因于CRAC通道的大型单通道事件的基础，这些事件被用作在天然细胞和重组表达系统中识别存储操作通道的工具。我们是否离识别难以捉摸的CRAC通道基因更近了一步(S)？TRPV6似乎是一个非常有吸引力的候选者，但支持它的主要论点之一是在二价自由溶液中的单通道电导，类似于在Magnum活跃的条件下报道的CRAC的电导。我们现在知道，在天然组织中，TRPV6的电导大约是CRAC的200倍。此外，目前还不清楚TRPV6是否为商店运营。对TRPV6的进一步研究，特别是在它明显形成多聚体的条件下，它的单通道电导是否仍然很高；与内源性存储操作的通道，以及它是否被各种存储耗尽协议激活，将有助于最终解决这个问题。(C)2002爱思唯尔科学有限公司。保留所有权利。
CRAC channels are key calcium conduits in both physiological and pathological states. Understanding how these channels are controlled is important as this will not only provide insight into a novel signal transduction pathway coupling intracellular stores to the channels in the plasma membrane, but might also be of clinical relevance. Determining the molecular identity of the CRAC channels will certainly be a,major step forward.Like all Ca2+-selective channels, CRAC channels lose their selectivity in divalent-free external solution to support large monovalent Na+ currents. This approach has provided new insight into channel permeation and selectivity, and identifies some interesting differences between CRAC channels and voltage-ope rated calcium channels (VOCCs). Studies in divalent-free solution are a double-edged sword, however. Electrophysiologists need to be wary because some of the conditions used to study /(CRAC) in divalent-free external solution, notably omission of Mg2+/Mg-ATP from the recording pipette solution, activates an additional current permeating through Mg2+-nucleotide-regulated metal ion current (MagNuM; TRPM7) channels.. This channel underlies the large single-channel events that have been attributed to CRAC channels in the past and which have been used to as a tool to identify store-operated channels in native cells and recombinant expression systems.Are we any closer to identifying the elusive CRAC channel gene(s)? TRPV6 seemed a very attractive candidate, but one of the main arguments supporting it was a single-channel conductance in divalent-free solution similar to that for CRAC reported under conditions where MagNuM is active. We now know that the conductance of TRPV6 is similar to200-fold larger than that of CRAC in native tissue. Moreover, it is unclear if TRPV6 is store-operated. Further work on TRPV6, particularly whether its single-channel conductance is still high under conditions where it apparently forms multimers; with endogenous store-operated channels, and whether it is activated by a variety of store depletion protocols, will be helpful in finally resolving this issue. (C) 2002 Elsevier Science Ltd. All rights reserved.