Cellular mechanisms of responses to hypoxia and hypercapnia in medullary neurons expressing a transcription factor, Phox2b

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K06946
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 46030:Function of nervous system-related
• Research Institution: Showa University
• Principal Investigator: Onimaru Hiroshi 昭和大学, 医学部, 客員教授 (30177258)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 高炭酸ガス応答 / 低酸素応答 / Phox2b / チロシン水酸化酵素 / 吻側腹外側延髄 / 新生児ラット

Outline of Final Research Achievements

We investigated membrane potential responses of cardio-respiratory neurons in the rostral ventrolateral medulla to hypoxic and hypercapnic stimulation in brainstem-spinal cord preparations from newborn rats. Responses were examined in the presence of TTX. Phox2b+/TH+ neurons indicated depolarization of 3.3 mV (n=15) in response to hypoxic stimulation but no significant change to hypercapnic stimulation. Phox2b+/TH- neurons did not respond to hypoxic stimulation but were depolarized by 6.1 mV (n=10) by hypercapnic stimulation. Membrane potential response of Phox2b-/TH- respiratory neurons to hypoxic stimulation varied; depolarization or hyperpolarization and the averaged change was -2.2 mV (n=19). The most noteworthy result in the present study is that Phox2b+/TH+ neurons (so called C1 adrenergic neurons) exhibited membrane depolarization as an intrinsic response to hypoxic stimulation, suggesting that they are central hypoxia-sensitive cells.

Free Research Field

神経生理学

Academic Significance and Societal Importance of the Research Achievements

今回の特に注目すべき研究結果は，Phox2b+/TH+ニューロン（いわゆるC1アドレナリンニューロン）が低酸素刺激に直接脱分極応答を示し，中枢性低酸素受容細胞であることが明らかになったことである．低酸素応答の分子機構については今後の課題として残されている．一方，呼吸性ニューロン（Phox2b-/TH-）では低酸素刺激に対しては脱分極を示すものと過分極を示すものがあった．過分極応答にはKATPチャネルが関与すると考えられた．C1アドレナリンニューロンは交感神経活動維持に重要な役割を持つ一方で，中枢低酸素受容器として働くことが示唆されたことは意義深い．