Acid-sensing ion channels (ASICs) are differentially modulated by anions dependent on their subunit composition.
Acid-sensing ion channels (ASICs) are differentially modulated by anions dependent on their subunit composition.
复制标题
酸敏感离子通道 (ASIC) 受阴离子的差异调节，具体取决于其亚基组成。
DOI：
10.1152/ajpcell.00216.2012
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Benson CJ.
中科院分区：
文献类型：
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作者：
Kusama N;Gautam M;Harding AM;Snyder PM;Benson CJ.
酸敏感离子通道（ASIC）是由细胞外质子门控的钠通道。ASIC 1a通道在细胞外结构域中具有亚基间Cl−结合位点，这些位点在ASIC亚基之间高度保守。我们以前发现，阴离子调节ASIC 1a门控通过这些网站。本研究采用全细胞膜片钳技术研究了阴离子取代对大鼠感觉神经元中天然ASICs和异源表达ASIC 2a和ASIC 3通道的影响。与ASIC 1a类似，阴离子调节其他ASIC通道的脱敏动力学。然而，与ASIC 1a不同，阴离子也调节了活化的pH依赖性。此外，不同阴离子对ASIC 2a和-3的调节效果的顺序与ASIC 1a的调节效果有很大不同。更令人惊讶的是，在ASIC 1a中形成亚基间Cl−结合位点的保守残基的突变仅部分消除了ASIC 2a的阴离子调节作用，并且对ASIC 3的阴离子调节没有影响。阴离子对大鼠背根神经节神经元中天然ASIC的影响模仿了异源表达的ASIC 1a/3异聚体通道中的影响。我们的数据表明，阴离子调节各种ASIC的性质，并依赖于亚基组成，和ASIC 2a和-3的调制机制是不同的ASIC 1a。我们推测Cl−对ASIC门控的调节是感知细胞外液成分变化的一种新机制。
Acid-sensing ion channels (ASICs) are sodium channels gated by extracellular protons. ASIC1a channels possess intersubunit Cl−-binding sites in the extracellular domain, which are highly conserved between ASIC subunits. We previously found that anions modulate ASIC1a gating via these sites. Here we investigated the effect of anion substitution on native ASICs in rat sensory neurons and heterologously expressed ASIC2a and ASIC3 channels by whole cell patch clamp. Similar to ASIC1a, anions modulated the kinetics of desensitization of other ASIC channels. However, unlike ASIC1a, anions also modulated the pH dependence of activation. Moreover, the order of efficacy of different anions to modulate ASIC2a and -3 was very different from that of ASIC1a. More surprising, mutations of conserved residues that form an intersubunit Cl−-binding site in ASIC1a only partially abrogated the effects of anion modulation of ASIC2a and had no effect on anion modulation of ASIC3. The effects of anions on native ASICs in rat dorsal root ganglion neurons mimicked those in heterologously expressed ASIC1a/3 heteromeric channels. Our data show that anions modulate a variety of ASIC properties and are dependent on the subunit composition, and the mechanism of modulation for ASIC2a and -3 is distinct from that of ASIC1a. We speculate that modulation of ASIC gating by Cl−is a novel mechanism to sense shifts in extracellular fluid composition.