Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China.
FASEB J. 2021 May;35(5):e21532. doi: 10.1096/fj.202002189R.
TWIK-related acid-sensitive potassium channels (TASKs)-like current was recorded in orexin neurons in the lateral hypothalamus (LH), which are essential in respiratory chemoreflex. However, the specific mechanism responsible for the pH-sensitivity remains elusive. Thus, we hypothesized that TASKs contribute to respiratory chemoreflex. In the present study, we found that TASK1 and TASK3 were expressed in orexin neurons. Blocking TASKs or microinjecting acid artificial cerebrospinal fluid (ACSF) in the LH stimulated breathing. In contrast, alkaline ACSF inhibited breathing, which was attenuated by blocking TASK1. Damage of orexin neurons attenuated the stimulatory effect on respiration caused by microinjection of acid ACSF (at a pH of 6.5) or TASKs antagonists. The orexinA-positive fiber and orexin type 1 receptor (OX1R) neurons were located in the nucleus tractus solitarius (NTS). The exciting effect of acidosis in the LH on respiration was inhibited by blocking OX1R of the NTS. Taken together, we conclude that orexin neurons sense the extracellular pH change through TASKs and regulate respiration by projecting to the NTS.
TWIK 相关酸敏感钾通道（TASKs）样电流在外侧下丘脑（LH）的食欲素神经元中被记录下来，这在呼吸化学反射中是必不可少的。然而，导致 pH 敏感性的具体机制仍不清楚。因此，我们假设 TASKs 有助于呼吸化学反射。在本研究中，我们发现 TASK1 和 TASK3 在食欲素神经元中表达。阻断 TASKs 或在 LH 中微注射酸性人工脑脊液（ACSF）会刺激呼吸。相反，碱性 ACSF 会抑制呼吸，而阻断 TASK1 则会减弱这种抑制作用。破坏食欲素神经元会减弱微注射酸性 ACSF（pH 值为 6.5）或 TASKs 拮抗剂对呼吸的刺激作用。orexinA 阳性纤维和 orexin 型 1 受体（OX1R）神经元位于孤束核（NTS）中。LH 中的酸中毒对呼吸的兴奋作用被 NTS 中的 OX1R 阻断所抑制。综上所述，我们得出结论，orexin 神经元通过 TASKs 感知细胞外 pH 值的变化，并通过投射到 NTS 来调节呼吸。
