Acid-sensing by airway afferent nerves

Area of Science:

• Respiratory Physiology
• Neuroscience
• Molecular Biology

Background:

• Acid inhalation or aspiration stimulates airway sensory nerves (C-fiber and Aδ afferents).
• This stimulation leads to airway irritation and defense reflexes such as cough and bronchoconstriction.
• Tissue acidosis in the respiratory tract, due to ischemia or inflammation (e.g., asthma exacerbation), affects airway nerves.

Purpose of the Study:

• To investigate the mechanisms of proton action on airway sensory neurons.
• To explore the role of acid-sensing ion channels and TRPV1 receptors in proton-evoked neuronal responses.
• To understand the contribution of these mechanisms to airway inflammatory diseases.

Main Methods:

• Electrophysiological recordings to characterize proton-evoked currents in airway sensory neurons.
• Investigating the involvement of acid-sensing ion channels and TRPV1 receptors.
• Examining the impact of inflammation on TRPV1 expression and sensitivity.

Main Results:

• Protons activate two distinct currents in airway sensory neurons: a transient current via acid-sensing ion channels and a sustained current via TRPV1.
• TRPV1 expression and/or sensitivity are upregulated in airway sensory nerves during chronic inflammation.
• These findings suggest a significant role for proton-evoked neuronal effects in airway inflammation.

Conclusions:

• Proton activation of airway sensory neurons occurs through acid-sensing ion channels and TRPV1.
• Upregulated TRPV1 in inflamed airways enhances sensitivity to protons.
• These mechanisms are implicated in the symptoms of airway inflammatory diseases.