Inhibitory effect of sulfur dioxide inhalation on Hering-Breuer inflation reflex in mice: role of voltage-gated potassium channels

被引:1
作者
Chan, Nai-Ju [1 ,2 ]
Hsu, Chun -Chun [2 ,3 ,4 ]
Lin, You Shuei [2 ,5 ]
Lin, Ruei-Lung [1 ]
Lee, Lu-Yuan [1 ]
机构
[1] Univ Kentucky, Dept Physiol, Med Ctr, Lexington, KY 40536 USA
[2] Taipei Med Univ, Grad Inst Med Sci, Coll Med, Taipei, Taiwan
[3] Taipei Med Univ, Coll Med, Sch Resp Therapy, Taipei, Taiwan
[4] Taipei Med Univ Hosp, Dept Internal Med, Div Pulm Med, Taipei, Taiwan
[5] Taipei Med Univ, Coll Med, Sch Med, Dept Physiol, Taipei, Taiwan
关键词
air pollutant; breathing pattern; lung; slowly adapting receptor; vagus nerve; 4-aminopyridine; CALCIUM-ION CHANNELS; PULMONARY; RECEPTORS; LUNG; 4-AMINOPYRIDINE; STRETCH; GENERATION; NERVES; VAGUS; BLOCK;
D O I
10.1152/japplphysiol.00714.2022
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Slowly adapting receptors (SARs), vagal mechanosensitive receptors located in the lung, play an important role in regulating the breathing pattern and Hering-Breuer inflation reflex (HBIR). Inhalation of high concentration of sulfur dioxide (SO2), a common environmental and occupational air pollutant, has been shown to selectively block the SAR activity in rabbits, but the mechanism underlying this inhibitory effect remained a mystery. We carried out this study to determine if inhalation of SO2 can inhibit the HBIR and change the eupneic breathing pattern, and to investigate further a possible involvement of voltage-gated K thorn channels in the inhibitory effect of SO2 on these vagal reflex-mediated responses. Our results showed 1) inhalation of SO2 (600 ppm; 8 min) consistently abolished both the phasic activity of SARs and their response to lung inflation in anesthetized, artificially venti-lated mice, 2) inhalation of SO2 generated a distinct inhibitory effect on the HBIR and induced slow deep breathing in anesthe-tized, spontaneously breathing mice, and these effects were reversible and reproducible in the same animals, 3) This inhibitory effect of SO2 was blocked by pretreatment with 4-aminopyridine (4-AP), a nonselective blocker of voltage-gated K thorn channel, and unaffected by pretreatment with its vehicle. In conclusion, this study suggests that this inhibitory effect on the baseline breathing pattern and the HBIR response was primarily mediated through the SO2-induced activation of voltage-gated K thorn chan-nels located in the vagal bronchopulmonary SAR neurons.NEW & NOTEWORTHY This study demonstrated that inhaled sulfur dioxide completely and reversibly abolished the activity of vagal bronchopulmonary slowly adapting receptors, significantly inhibited the apneic response to lung inflation, and induced slow deep breathing in anesthetized mice. More importantly, our results further suggested that this inhibitory effect was medi-ated through an action of sulfur dioxide and its derivatives on the voltage-gated potassium channels expressed in the slowly adapting receptor sensory neurons innervating the lung.
引用
收藏
页码:1075 / 1082
页数:8
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