TASK1 and TASK3 Are Coexpressed With ASIC1 in the Ventrolateral Medulla and Contribute to Central Chemoreception in Rats.
TASK1 and TASK3 Are Coexpressed With ASIC1 in the Ventrolateral Medulla and Contribute to Central Chemoreception in Rats.
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TASK1 和 TASK3 在腹外侧髓质中与 ASIC1 共表达，并有助于大鼠的中枢化学感受
DOI：
10.3389/fncel.2018.00285
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发表时间：
2018
影响因子：
5.3
通讯作者：
Shen L
中科院分区：
文献类型：
--
作者：
Wang X;Guan R;Zhao X;Zhu D;Song N;Shen L
延髓腹外侧区（VLM），包括外侧巨细胞旁核（LPGi）和头端VLM（RVLM），通常被认为是化学敏感区。然而，在VLM的化学感受的具体机制仍然难以捉摸。酸敏感离子通道（ASIC）是一类电压非依赖性质子门控阳离子通道，可被外部pH降低激活，引起Na+内流并诱导神经元兴奋性。TWIK-related acid-sensitive potassium channels（TASK）是另一组pH敏感性通道的成员;与AISIC相反，它们可以被pH升高刺激，并且在生理范围内被pH降低抑制。我们以前的研究表明，ASIC参与化学感受。本研究的目的是探讨TASK是否参与VLM神经元的酸敏感性，从而与ASIC合作。我们的研究表明，TASKs，包括TASK 1和TASK 3，在VLM神经元中与ASIC 1共定位。通过在VLM内微量注射非选择性TASK拮抗剂布比卡因（BUP）、特异性TASK 1拮抗剂花生四烯酸（AEA）或特异性TASK 3拮抗剂钌红（RR）来阻断TASK，可增加膈神经整合放电（iPND），缩短吸气时间（Ti），增强呼吸驱动（iPND/Ti）。此外，微量注射pH7.0或6.5的人工脑脊液（ACSF）可延长Ti，增加iPND和增强呼吸驱动，而ASIC拮抗剂阿米洛利（AMI）可抑制这些作用。相反，微量注射碱性ACSF可降低iPND和呼吸驱动，而AEA则可抑制iPND和呼吸驱动。综上所述，我们的数据表明，TASK 1和TASK 3与ASIC 1在VLM中共表达。此外，TASK 1和TASK 3通过相互协调来感知局部pH变化，从而有助于呼吸的中枢调节;这些结果表明VLM的新的化学敏感性机制。
The ventrolateral medulla (VLM), including the lateral paragigantocellular nucleus (LPGi) and rostral VLM (RVLM), is commonly considered to be a chemosensitive region. However, the specific mechanism of chemoreception in the VLM remains elusive. Acid-sensing ion channels (ASICs), a family of voltage-independent proton-gated cation channels, can be activated by an external pH decrease to cause Na+ entry and induce neuronal excitability. TWIK-related acid-sensitive potassium channels (TASKs) are members of another group of pH-sensitive channels; in contrast to AISICs, they can be stimulated by pH increases and are inhibited by pH decreases in the physiological range. Our previous study demonstrated that ASICs take part in chemoreception. The aims of this study are to explore whether TASKs participate in the acid sensitivity of neurons in the VLM, thereby cooperating with ASICs. Our research demonstrated that TASKs, including TASK1 and TASK3, are colocalized with ASIC1 in VLM neurons. Blocking TASKs by microinjection of the non-selective TASK antagonist bupivacaine (BUP), specific TASK1 antagonist anandamide (AEA) or specific TASK3 antagonist ruthenium red (RR) into the VLM increased the integrated phrenic nerve discharge (iPND), shortened the inspiratory time (Ti) and enhanced the respiratory drive (iPND/Ti). In addition, microinjection of artificial cerebrospinal fluid (ACSF) at a pH of 7.0 or 6.5 prolonged Ti, increased iPND and enhanced respiratory drive, which were inhibited by the ASIC antagonist amiloride (AMI). By contrast, microinjection of alkaline ACSF decreased iPND and respiratory drive, which were inhibited by AEA. Taken together, our data suggest that TASK1 and TASK3 are coexpressed with ASIC1 in the VLM. Moreover, TASK1 and TASK3 contribute to the central regulation of breathing by coordinating with each other to perceive local pH changes; these results indicate a novel chemosensitive mechanism of the VLM.
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影响因子：
2.3
作者：
Corcoran, Andrea E.;Hodges, Matthew R.;Wu, Yuanming;Wang, Wengang;Wylie, Christie J.;Deneris, Evan S.;Richerson, George B.
通讯作者：
Richerson, George B.
影响因子：
--
作者：
Holzer, Peter
通讯作者：
Holzer, Peter
DOI：
10.1007/s00424-014-1633-9
发表时间：
2015-05
期刊：
Pflugers Archiv : European journal of physiology
影响因子：
--
作者：
Bayliss DA;Barhanin J;Gestreau C;Guyenet PG
通讯作者：
Guyenet PG
影响因子：
5.5
作者：
de la Rosa, DA;Krueger, SR;Canessa, CM
通讯作者：
Canessa, CM
DOI：
10.1016/s0034-5687(01)00288-2
发表时间：
2001-12-01
期刊：
RESPIRATION PHYSIOLOGY
影响因子：
--
作者：
Bayliss, DA;Talley, EM;Lei, QB
通讯作者：
Lei, QB