Electrophysiological properties of the dorsal motor nucleus of the vagus motoneurones controlling airway mucus secretion in rats.

The parasympathetic efferent innervation to the respiratory airways controls bronchoconstriction and mucus secretion. It is known that the parasympathetic respiratory motoneurones (PRMNs) projecting to the airways are located in the nucleus ambiguus (NA) and dorsal motor nucleus of the vagus (DMV). Although NA PRMNs are known to regulate bronchoconstriction in both physiological and pathological conditions, the electrophysiological properties of DMV PRMNs and their functional role in regulating the airways are not entirely clear. Retrograde labelling, neuronal and ventilatory recordings, optogenetics, chemogenetics, and histological and molecular analyses in vitro and in vivo preparations of rats were performed to evaluate the electrophysiological characteristics controlling the activity of DMV PRMNs and their role in airway mucus secretion. DMV PRMNs present K+-dominated leak currents, mediated by two-pore domain TWIK-2 channels, which regulate their resting membrane potential, firing frequency and excitation by acidosis. Acidosis also reduces synaptic inhibition to these motoneurones and activates astrocytes in the DMV. Furthermore, optogenetic activation of astrocytes induced action potentials in DMV PRMNs, mediated by glutamatergic NMDA receptor excitation. Finally, chemogenetic activation of DMV PRMNs evoked mucus secretion in respiratory airways and increases sighing, without affecting inflammatory cell infiltration, pulmonary ventilation, oxygen consumption or heart rate. Therefore, our data demonstrate that TWIK-2 leak channels and astrocytes signalling regulate the activity of DMV PRMNs and their role in airway mucus secretion of rats. KEY POINTS: Parasympathetic respiratory motoneurones (PRMNs) of the dorsal motor nucleus of the vagus (DMV) present K+-dominated leak currents, mediated by TWIK-2 channels, regulating their resting membrane potential, firing frequency and excitation by acidosis. Acidosis also reduces synaptic inhibition to DMV PRMNs and activates astrocytes in the DMV. Activation of DMV astrocytes induced action potentials in PRMNs, mediated by glutamatergic NMDA receptor excitation. Activation of DMV PRMNs evoked mucus secretion in respiratory airways and increased sighing, without affecting pulmonary ventilation, oxygen consumption or heart rate. TWIK-2 leak channels and astrocytes signalling regulate the activity of DMV PRMNs and their role in airway mucus secretion of rats.