Pichard L E, Crainiceanu C M, Pashai P, Kostuk E W, Fujioka A, Shirahata M
Department of Environmental Health Sciences, Johns Hopkins University, Baltimore, MD, USA.
Adv Exp Med Biol. 2015;860:325-33. doi: 10.1007/978-3-319-18440-1_37.
The aim of this study was to explore the role of BK channels in the hypoxic sensitivity of the in vivo murine carotid body (CB). Four strains of mice (DBA/2J, A/J, BKα1 knockout and BKα1 wild type - FVB background) were used. The mice were anesthetized, paralyzed and mechanically ventilated (PaCO(2) ~ 35 mmHg, PO(2) > 300 mmHg). We measured carotid sinus nerve (CSN) activity during three gas challenges (F(I)O(2): 0.21, 0.15 and 0.10). CSN activity was analyzed with time-variant spectral analysis with frequency domain conversion (Fast Fourier Transforms). Afferent CSN activity increased with lowering F(I)O(2) in the DBA/2J, BKKO and BKWT mice with the most robust response in 600-800 frequencies. No substantial changes were observed in the A/J mice. Although maximal neural output was similar between the BKKO and BKWT mice, the BKWT had a higher early response compared to BKKO. Thus, BK channels may play a role in the initial response of the CB to hypoxia. The contribution of BKβ subunits or the importance of frequency specific responses was unable to be determined by the current study.
本研究的目的是探讨BK通道在体内小鼠颈动脉体(CB)低氧敏感性中的作用。使用了四株小鼠(DBA/2J、A/J、BKα1基因敲除小鼠和BKα1野生型小鼠 - FVB背景)。小鼠经麻醉、麻痹并进行机械通气(动脉血二氧化碳分压~35 mmHg,动脉血氧分压>300 mmHg)。在三种气体刺激(吸入氧分数:0.21、0.15和0.10)期间,我们测量了颈动脉窦神经(CSN)的活动。采用频域转换的时变频谱分析(快速傅里叶变换)对CSN活动进行分析。在DBA/2J、BK基因敲除小鼠和BK野生型小鼠中,随着吸入氧分数降低,传入CSN活动增加,在600 - 800频率时反应最为强烈。在A/J小鼠中未观察到明显变化。虽然BK基因敲除小鼠和BK野生型小鼠的最大神经输出相似,但与BK基因敲除小鼠相比,BK野生型小鼠的早期反应更高。因此,BK通道可能在CB对低氧的初始反应中发挥作用。目前的研究无法确定BKβ亚基的作用或频率特异性反应的重要性。