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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >TRPM5 is a transient Ca~(2+)-activated cation channel responding to rapid changes in [Ca~(2+)]_i
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TRPM5 is a transient Ca~(2+)-activated cation channel responding to rapid changes in [Ca~(2+)]_i

机译：TRPM5是瞬变的Ca〜（2+）活化阳离子通道，响应[Ca〜（2 +）] _ i的快速变化

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摘要

Transient receptor potential (TRP) proteins are a diverse family of proteins with structural features typical of ion channels. TRPM5, a member of the TRPM subfamily, plays an important role in taste receptors, although its activation mechanism remains controversial and its function in signal transduction is unknown. Here we characterize the functional properties of heterologously expressed human TRPM5 in HEK-293 cells. TRPM5 displays characteristics of a calcium-activated, nonselective cation channel with a unitary conductance of 25 pS. TRPM5 is a monovalent-specific, nonselective cation channel that carries Na~+, K~+, and Cs~+ ions equally well, but not Ca~(2+) ions. It is directly activated by [Ca~(2+)]_i at concentrations of 0.3-1 μM, whereas higher concentrations are inhibitory, resulting in a bell-shaped dose-response curve. It activates and deactivates rapidly even during sustained elevations in [Ca~(2+)]_i, thereby inducing a transient membrane depolarization. TRPM5 does not simply mirror levels of [Ca~(2+)]_i, but instead responds to the rate of change in [Ca~(2+)]_i in that it requires rapid changes in [Ca~(2+)]_i to generate significant whole-cell currents, whereas slow elevations in [Ca~(2+)]_i to equivalent levels are ineffective. Moreover, we demonstrate that TRPM5 is not limited to taste signal transduction, because we detect the presence of TRPM5 in a variety of tissues and we identify endogenous TRPM5-like currents in a pancreatic beta cell line. TRPM5 can be activated physiologically by inositol 1,4,5-trisphos-phate-producing receptor agonists, and it may therefore couple intracellular Ca~(2+) release to electrical activity and subsequent cellular responses.
机译：瞬态受体电位（TRP）蛋白质是具有离子通道典型结构特征的多种蛋白质家族。 TRPM5是TRPM家族的成员，在味觉受体中起着重要作用，尽管其激活机制仍存在争议，其在信号转导中的功能尚不清楚。在这里，我们表征HEK-293细胞中异源表达的人类TRPM5的功能特性。 TRPM5显示钙激活的非选择性阳离子通道的特性，单位电导为25 pS。 TRPM5是单价特异性的非选择性阳离子通道，可同样好地携带Na〜+，K〜+和Cs〜+离子，但不携带Ca〜（2+）离子。它在浓度为0.3-1μM时被[Ca〜（2 +）] _ i直接激活，而更高的浓度则具有抑制作用，从而形成钟形的剂量反应曲线。即使在[Ca〜（2 +）] _ i持续升高期间，它也会迅速激活和失活，从而引起瞬时膜去极化。 TRPM5不只是镜像[Ca〜（2 +）] _ i的电平，而是响应[Ca〜（2 +）] _ i的变化速率，因为它需要[Ca〜（2 +）] _ i的快速变化。 _i产生显着的全细胞电流，而[Ca〜（2 +）] _ i中缓慢升高到等效水平无效。此外，我们证明TRPM5不限于味觉信号转导，因为我们检测到TRPM5在多种组织中的存在，并且在胰腺β细胞系中鉴定出内源性TRPM5样电流。 TRPM5可以被肌醇1,4,5-三膦磷酸盐生成受体激动剂生理激活，因此可以将细胞内Ca〜（2+）释放耦合到电活动和随后的细胞反应中。

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