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

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⁺ 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 ventilated mice, 2) inhalation of SO₂ generated a distinct inhibitory effect on the HBIR and induced slow deep breathing in anesthetized, 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⁺ 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⁺ channels located in the vagal bronchopulmonary SAR neurons.