Acid-sensing ion channels are expressed in the ventrolateral medulla and contribute to central chemoreception.

Acid-sensing ion channels are expressed in the ventrolateral medulla and contribute to central chemoreception.
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酸敏感离子通道在腹外侧延髓中表达,有助于中枢化学感受

DOI:
10.1038/srep38777
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发表时间:
2016-12-09
期刊:
影响因子:
4.6
通讯作者:
Shen L
Shen L
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Song N;Guan R;Jiang Q;Hassanzadeh CJ;Chu Y;Zhao X;Wang X;Yang D;Du Q;Chu XP;Shen L

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在延髓腹外侧区,酸敏感离子通道(ASICs)的作用仍不确定。在这里,我们发现ASIC1a和ASIC2在大鼠延髓中广泛表达,新生期的表达水平高于成年期。这两个ASIC亚基共同定位于中脑神经元。此外,pH降低在延髓中触发了典型的ASIC型电流,包括VLm。这些电流的PH50值为6.6,可被阿米洛利阻断。基于它们对psalmotox1(PcTx1)和锌的敏感性,同构体ASIC1a和异构体ASIC1a/2通道可能是小鼠延髓内酸介导的电流的原因。在ASIC1−/−小鼠的VLm神经元上,由pH 5触发的ASIC电流消失,但在ASIC2−/−小鼠的VLm神经元上无此现象。延髓内ASICs的激活也触发了神经元的兴奋。此外,向VLm内微量注射pH为6.5的人工脑脊液,可增加大鼠的综合膈神经放电、吸气时间和呼吸驱动。阿米洛利和PcTx1均可抑制酸诱导的呼吸刺激作用。总体而言,我们的数据表明ASIC在包括VLM在内的延髓中高度表达,VLM中ASIC的激活有助于中枢化学接收。
The role of acid-sensing ion channels (ASICs) in the ventrolateral medulla (VLM) remains uncertain. Here, we found that ASIC1a and ASIC2 are widely expressed in rat medulla, and the expression level is higher at neonatal stage as compared to adult stage. The two ASIC subunits co-localized in medualla neurons. Furthermore, pH reduction triggered typical ASIC-type currents in the medulla, including the VLM. These currents showed a pH50 value of 6.6 and were blocked by amiloride. Based on their sensitivity to psalmotoxin 1 (PcTx1) and zinc, homomeric ASIC1a and heteromeric ASIC1a/2 channels were likely responsible for acid-mediated currents in the mouse medulla. ASIC currents triggered by pH 5 disappeared in the VLM neurons from ASIC1−/−, but not ASIC2−/− mice. Activation of ASICs in the medulla also triggered neuronal excitation. Moreover, microinjection of artificial cerebrospinal fluid at a pH of 6.5 into the VLM increased integrated phrenic nerve discharge, inspiratory time and respiratory drive in rats. Both amiloride and PcTx1 inhibited the acid-induced stimulating effect on respiration. Collectively, our data suggest that ASICs are highly expressed in the medulla including the VLM, and activation of ASICs in the VLM contributes to central chemoreception.
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