Electrophysiological Properties and Morphology of Cardiac and Pulmonary Motoneurons within the Dorsal Motor Nucleus of the Vagus of Rats.

The dorsal motor nucleus of the vagus (DMV) contains parasympathetic motoneurons that project to the heart and lungs. These motoneurons control ventricular excitability/contractility and airways secretions/blood flow, respectively. However, their electrophysiological properties, morphology and synaptic input activity remain unknown. One important ionic current described in DMV motoneurons controlling their electrophysiological behaviour is the A-type mediated by voltage-dependent K+ (Kv) channels. Thus, we compared the electrophysiological properties, synaptic activity, morphology, A-type current density, and single cell expression of Kv subunits, that contribute to macroscopic A-type currents, between DMV motoneurons projecting to either the heart or lungs of adult male rats. Using retrograde labelling, we visualized distinct DMV motoneurons projecting to the heart or lungs in acutely prepared medullary slices. Subsequently, whole cell recordings, morphological reconstruction and single motoneuron qRT-PCR studies were performed. DMV pulmonary motoneurons were more depolarized, electrically excitable, presented higher membrane resistance, broader action potentials and received greater excitatory synaptic inputs compared to cardiac DMV motoneurons. These differences were in part due to highly branched dendritic complexity and lower magnitude of A-type K+ currents. By evaluating expression of channels that mediate A-type currents from single motoneurons, we demonstrated a lower level of Kv4.2 in pulmonary versus cardiac motoneurons, whereas Kv4.3 and Kv1.4 levels were similar. Thus, with the distinct electrical, morphological, and molecular properties of DMV cardiac and pulmonary motoneurons, we surmise that these cells offer a new vista of opportunities for genetic manipulation providing improvement of parasympathetic function in cardiorespiratory diseases such heart failure and asthma.

Heightened respiratory-parasympathetic coupling to airways in the spontaneously hypertensive rat.

KEY POINTS: Carotid body (CB) chemoreceptors are hyperactive in hypertension, and their acute activation produces bronchoconstriction. We show that the respiratory-modulated bronchiolar tone, pulmonary parasympathetic efferent activity, and the firing frequency and synaptic excitation of bronchoconstrictor motoneurones in the nucleus ambiguus were all enhanced in spontaneous hypertensive (SH) rats. In SH rats, CB denervation reduced the respiratory-related parasympathetic-mediated bronchoconstrictor tone to levels seen in normotensive rats. Chemoreflex evoked bronchoconstrictor tone was heightened in SH versus normotensive rats. The intrinsic electrophysiological properties and morphology of bronchoconstrictor motoneurones were similar across rat strains. The heightened respiratory modulation of parasympathetic-mediated bronchoconstrictor tone to the airways in SH rats is caused by afferent drive from the CBs. ABSTRACT: Much research has described heightened sympathetic activity in hypertension and diminished parasympathetic tone, especially to the heart. The carotid body (CB) chemoreceptors exhibit hyperreflexia and are hyperactive, providing excitatory drive to sympathetic networks in hypertension. Given that acute CB activation produces reflex evoked bronchoconstriction via activation of parasympathetic vagal efferents, we hypothesised that the parasympathetic bronchoconstrictor activity is enhanced in spontaneously hypertensive (SH) rats and that this is dependent on CB inputs. In situ preparations of Wistar and SH rats were used in which bronchiolar tone, the pulmonary branch of the vagus (pVN) and phrenic nerves were recorded simultaneously; whole cell patch clamp recordings of bronchoconstrictor vagal motoneurones were also made from the nucleus ambiguus. Bronchiolar tone, pVN and bronchoconstrictor motoneurones were respiratory modulated and this modulation was enhanced in SH rats. These differences were all eliminated after CB denervation. Stimulation of the CBs increased the phrenic frequency that caused a summation of the respiratory-related increases in pVN, resulting in the development of bronchoconstrictor tone. This tone was exaggerated in SH rats. The enhanced respiratory-parasympathetic coupling to airways in SH rats was not due to differences in the intrinsic electrophysiological properties of bronchoconstrictor motoneurones but reflected heightened pre-inspiratory- and inspiratory-related synaptic drive. In summary, in SH rats the phasic respiratory modulation of parasympathetic tone to the airways is elevated and the greater development of this bronchoconstrictor tone is caused by the heightened afferent drive originating from the CBs. Thus, targeting the CBs may prove effective for increasing lower airway patency.

Chronic intermittent hypoxia increases excitability and synaptic excitation of protrudor and retractor hypoglossal motoneurones.

KEY POINTS: Dysfunctions in the hypoglossal control of tongue extrinsic muscles are implicated in obstructive sleep apnoea (OSA) syndrome. Chronic intermittent hypoxia (CIH), an important feature of OSA syndrome, produces deleterious effects on the motor control of oropharyngeal resistance, but whether the hypoglossal motoneurones innervating the tongue extrinsic muscles are affected by CIH is unknown. We show that CIH enhanced the respiratory-related activity of rat hypoglossal nerve innervating the protrudor and retractor tongue extrinsic muscles. Intracellular recordings revealed increases in respiratory-related firing frequency and synaptic excitation of inspiratory protrudor and retractor hypoglossal motoneurones after CIH. CIH also increased their intrinsic excitability, depolarised resting membrane potential and reduced K+ -dominated leak conductance. CIH affected the breathing-related synaptic control and intrinsic electrophysiological properties of protrudor and retractor hypoglossal motoneurones to optimise the neural control of oropharyngeal function. ABSTRACT: Inspiratory-related tongue movements and oropharyngeal motor actions are controlled mainly by the protrudor and retractor extrinsic tongue muscles, which are innervated by the hypoglossal motoneurones. Chronic intermittent hypoxia (CIH), an important feature of obstructive sleep apnoea syndrome, produces detrimental effects on the contractile function of the tongue extrinsic muscles and the medullary inspiratory network of rodents. However, the impact of the CIH on the electrophysiological properties of protrudor and retractor hypoglossal motoneurones has not been described before. Using nerves and intracellular recordings in in situ preparation of rats (5 weeks old), we tested the hypothesis that CIH (FiO2 of 0.06, SaO2 74%, during 30-40 s, every 9 min, 8 h/day for 10 days) increases the intrinsic excitability of protrudor and retractor motoneurones from the hypoglossal motor nucleus of rats. Recordings of hypoglossal nerve, before its bifurcation to innervate the tongue protrudor and retractor muscles, revealed that CIH enhances its pre-inspiratory, simultaneously with the presence of active expiration, and inspiratory activities. These changes were mediated by increases in the respiratory-related firing frequency and synaptic excitation of inspiratory protrudor and retractor hypoglossal motoneurones. Besides, CIH increases their intrinsic excitability and depolarises resting membrane potential by reducing a K+ -dominated leak conductance. In conclusion, CIH enhances the respiratory-related neural control of oropharyngeal function of rats by increasing the synaptic excitation, intrinsic excitability, and reducing leak conductance in both protrudor and retractor hypoglossal motoneurones. We propose that these network and cellular changes are important to optimise the oropharyngeal resistance in conditions related to intermittent hypoxia.