Acid-sensing ion channels contribute to chemosensitivity of breathing-related neurons of the nucleus of the solitary tract
Acid-sensing ion channels contribute to chemosensitivity of breathing-related neurons of the nucleus of the solitary tract
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DOI：
10.1113/jphysiol.2012.232470
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发表时间：
2012-10-01
影响因子：
5.5
通讯作者：
Martina, Marco
中科院分区：
文献类型：
--
作者：
Huda, Rafiq;Pollema-Mays, Sarah L.;Martina, Marco
关键点孤束核（nucleus tractus solitarius，NTS）的一个神经元子集显示出对生理范围（7.4至7.0）内pH变化的反应，这是由酸敏感离子通道（ASIC）介导的。这些反应神经元似乎在NTS的背侧聚集。ASIC 1和ASIC 2转录本在NTS中表达。投射到腹侧呼吸柱的NTS神经元显示ASIC介导的对轻度pH挑战的反应，并可能调节呼吸反应。将ASIC抑制剂阿米洛利注射到NTS中可短暂抑制高碳酸血症麻醉大鼠的呼吸频率。摘要中枢pH化学敏感性的细胞机制在很大程度上仍不清楚。孤束核（NTS）整合外周传入与中枢通路控制呼吸; NTS神经元作为中央化学传感器的功能，但只有有限的信息存在有关的离子机制。酸敏感离子通道（ASIC）介导伤害性末梢的化学敏感性，其中pH值类似于6.5在炎症中并不罕见，但也在整个大脑中大量表达，其中pH值受到严格调节，它们的作用不太清楚。在这里，我们测试的假设，ASIC的表达在NTS神经元，并有助于内在的化学敏感性和呼吸控制。在急性大鼠NTS切片的电生理记录中，近似40%的NTS神经元对生理酸化（pH 7.0）产生短暂的去极化反应。这种反应也存在于分离的神经元中，这表明了一种内在机制。在电压钳记录切片，pH值从7.4下降到7.0诱导ASIC样内向电流（阻断100类似于μ m阿米洛利）在类似于40%的NTS神经元，而在pH值类似于=类似于6.5这些电流被检测到在所有的神经元测试; RT-PCR显示ASIC 1的表达，不太丰富，ASIC 2的NTS。充满染料的神经元的解剖学分析表明，ASIC依赖的化学敏感细胞（细胞响应pH 7.0）集群背侧的NTS。采用腹侧呼吸柱的体内逆行标记，90%（9/10）的标记神经元对pH 7.0显示ASIC样反应，表明ASIC电流有助于呼吸控制。因此，向NTS注射阿米洛利会减少动脉升高的麻醉大鼠的膈神经活动。
Key point A subset of neurons of the nucleus of the solitary tract (nucleus tractus solitarius, NTS) show a response to changes in pH within the physiological range (7.4 to 7.0) that is mediated by acid sensing ion channels (ASICs). These responder neurons appear to cluster dorsally in the NTS. ASIC1 and ASIC2 transcripts are expressed in the NTS. NTS neurons projecting to the ventral respiratory column show ASIC-mediated responses to mild pH challenges and may modulate the respiratory response to . Injection of the ASIC inhibitor amiloride into the NTS transiently depresses breathing frequency in hypercapnic anaesthetized rats. Abstract Cellular mechanisms of central pH chemosensitivity remain largely unknown. The nucleus of the solitary tract (NTS) integrates peripheral afferents with central pathways controlling breathing; NTS neurons function as central chemosensors, but only limited information exists concerning the ionic mechanisms involved. Acid-sensing ion channels (ASICs) mediate chemosensitivity in nociceptive terminals, where pH values similar to 6.5 are not uncommon in inflammation, but are also abundantly expressed throughout the brain where pH is tightly regulated and their role is less clear. Here we test the hypothesis that ASICs are expressed in NTS neurons and contribute to intrinsic chemosensitivity and control of breathing. In electrophysiological recordings from acute rat NTS slices, similar to 40% of NTS neurons responded to physiological acidification (pH 7.0) with a transient depolarization. This response was also present in dissociated neurons suggesting an intrinsic mechanism. In voltage clamp recordings in slices, a pH drop from 7.4 to 7.0 induced ASIC-like inward currents (blocked by 100 similar to mu m amiloride) in similar to 40% of NTS neurons, while at pH similar to=similar to 6.5 these currents were detected in all neurons tested; RT-PCR revealed expression of ASIC1 and, less abundantly, ASIC2 in the NTS. Anatomical analysis of dye-filled neurons showed that ASIC-dependent chemosensitive cells (cells responding to pH 7.0) cluster dorsally in the NTS. Using in vivo retrograde labelling from the ventral respiratory column, 90% (9/10) of the labelled neurons showed an ASIC-like response to pH 7.0, suggesting that ASIC currents contribute to control of breathing. Accordingly, amiloride injection into the NTS reduced phrenic nerve activity of anaesthetized rats with an elevated arterial .