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Modulation of hypoglossal motoneuron excitability by NK1 receptor activation in neonatal mice in vitro
Author(s) -
Yasuda Kouichi,
Robinson Dean M.,
Selvaratnam Subramaniam R.,
Walsh Carmen W.,
McMorland Angus J. C.,
Funk Gregory D.
Publication year - 2001
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2001.00447.x
Subject(s) - agonist , chemistry , current clamp , hyperpolarization (physics) , medicine , substance p , excitatory postsynaptic potential , receptor , endocrinology , nk1 receptor antagonist , patch clamp , neuroscience , biology , neuropeptide , stereochemistry , nuclear magnetic resonance spectroscopy
1 The effects of substance P (SP), acting at NK1 receptors, on the excitability and inspiratory activity of hypoglossal (XII) motoneurons (MNs) were investigated using rhythmically active medullary‐slice preparations from neonatal mice (postnatal day 0‐3). 2 Local application of the NK1 agonist [SAR 9 ,Met (O 2 ) 11 ]‐SP (SP NK1 ) produced a dose‐dependent, spantide‐ (a non‐specific NK receptor antagonist) and GR82334‐(an NK1 antagonist) sensitive increase in inspiratory burst amplitude recorded from XII nerves. 3 Under current clamp, SP NK1 significantly depolarized XII MNs, potentiated repetitive firing responses to injected currents and produced a leftward shift in the firing frequency‐current relationships without affecting slope. 4 Under voltage clamp, SP NK1 evoked an inward current and increased input resistance, but had no effect on inspiratory synaptic currents. SP NK1 currents persisted in the presence of TTX, were GR82334 sensitive, were reduced with hyperpolarization and reversed near the expected E K . 5 Effects of the α 1 ‐noradrenergic receptor agonist phenylephrine (PE) on repetitive firing behaviour were virtually identical to those of SP NK1 . Moreover, SP NK1 currents were completely occluded by PE, suggesting that common intracellular pathways mediate the actions of NK1 and α 1 ‐noradrenergic receptors. In spite of the similar actions of SP NK1 and PE on XII MN responses to somally injected current, α 1 ‐noradrenergic receptor activation potentiated inspiratory synaptic currents and was more than twice as effective in potentiating XII nerve inspiratory burst amplitude. 6 GR82334 reduced XII nerve inspiratory burst amplitude and generated a small outward current in XII MNs. These observations, together with the first immunohistochemical evidence in the newborn for SP immunopositive terminals in the vicinity of SP NK1 ‐sensitive inspiratory XII MNs, support the endogenous modulation of XII MN excitability by SP. 7 In contrast to phrenic MNs (Ptak et al. 2000), blocking NMDA receptors with AP5 had no effect on the modulation of XII nerve activity by SP NK1 . 8 In conclusion, SP NK1 modulates XII motoneuron responses to inspiratory drive primarily through inhibition of a resting, postsynaptic K + leak conductance. The results establish the functional significance of SP in controlling upper airway tone during early postnatal life and indicate differential modulation of motoneurons controlling airway and pump muscles by SP.