An acid‐sensing ion channel from shark (Squalus acanthias) mediates transient and sustained responses to protons
An acid‐sensing ion channel from shark (Squalus acanthias) mediates transient and sustained responses to protons
复制标题
鲨鱼（Squalus acanthias）的酸感应离子通道介导对质子的瞬时和持续反应
DOI：
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
S. Gründer
中科院分区：
文献类型：
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作者：
Andreas Springauf;S. Gründer
酸敏感离子通道（ASIC）是质子门控Na+通道。它们与突触传递、疼痛性酸中毒的检测以及可能的酸味有关。典型的ASIC电流是一种短暂的、完全脱敏的电流，可以被利尿剂阿米洛利阻断。ASIC存在于脊索动物中，但在其他动物中不存在。它们已经从尾索动物、无颌脊椎动物、软骨鲨鱼和硬骨鱼、鸡和不同的哺乳动物中克隆出来。引人注目的是，迄今为止，所有的ASIC的特点是从尾索动物，无颌脊椎动物和鲨鱼不门控质子，这表明质子门控进化相对较晚的硬骨鱼和原始的ASIC有一个不同的和未知的门控机制。最近，已经确定了对大鼠ASIC1a的质子门控至关重要的氨基酸。这些残基在鲨鱼ASIC1b（sASIC1b）中是完全保守的，这促使我们重新评估sASIC1b的质子敏感性。在这里，我们表明，与以前的研究结果相反，sASIC1b确实是由质子门控的，在pH 6.0时具有半最大激活。sASIC1b快速但不完全脱敏，有效地编码瞬时以及持续的质子信号。我们的研究结果表明，保守的质子门控关键的氨基酸可以预测ASIC的质子敏感性和增加我们的理解ASIC的演变。
Acid‐sensing ion channels (ASICs) are proton‐gated Na+ channels. They are implicated in synaptic transmission, detection of painful acidosis, and possibly sour taste. The typical ASIC current is a transient, completely desensitizing current that can be blocked by the diuretic amiloride. ASICs are present in chordates but are absent in other animals. They have been cloned from urochordates, jawless vertebrates, cartilaginous shark and bony fish, from chicken and different mammals. Strikingly, all ASICs that have so far been characterized from urochordates, jawless vertebrates and shark are not gated by protons, suggesting that proton gating evolved relatively late in bony fish and that primitive ASICs had a different and unknown gating mechanism. Recently, amino acids that are crucial for the proton gating of rat ASIC1a have been identified. These residues are completely conserved in shark ASIC1b (sASIC1b), prompting us to re‐evaluate the proton sensitivity of sASIC1b. Here we show that, contrary to previous findings, sASIC1b is indeed gated by protons with half‐maximal activation at pH 6.0. sASIC1b desensitizes quickly but incompletely, efficiently encoding transient as well as sustained proton signals. Our results show that the conservation of the amino acids crucial for proton gating can predict proton sensitivity of an ASIC and increase our understanding of the evolution of ASICs.
影响因子：
4.8
作者：
G. Mckhann
通讯作者：
G. Mckhann