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Protein kinase G‐dependent mechanisms modulate hypoglossal motoneuronal excitability and long‐term facilitation
Author(s) -
Saywell Shane A.,
Babiec Walter E.,
Neverova Natalia V.,
Feldman Jack L.
Publication year - 2010
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 - 10.1113/jphysiol.2010.194209
Subject(s) - chemistry , ampa receptor , neuroscience , postsynaptic potential , protein kinase a , synaptic plasticity , inhibitory postsynaptic potential , medicine , endocrinology , glutamate receptor , biology , receptor , kinase , biochemistry
Since protein kinase‐dependent modulation of motoneuronal excitability contributes to adaptive changes in breathing, we hypothesized that cGMP‐dependent pathways activating protein kinase G (PKG) modulate motoneuronal inspiratory drive currents and long‐term plasticity. In a medullary slice preparation from neonatal rat (postnatal days 0–4) generating spontaneous respiratory‐related rhythm, hypoglossal (XII) motoneuronal inspiratory drive currents and respiratory‐related XII nerve activity were recorded. Focal application of a PKG activator, 8‐bromoguanosine‐3′,5′‐cyclomonophosphate (8‐Br‐cGMP), to voltage‐clamped XII motoneurones decreased inspiratory drive currents. In the presence of tetrodotoxin (TTX), 8‐Br‐cGMP decreased the exogenous postsynaptic inward currents induced by focal application of AMPA. Intracellular dialysis of XII motoneurones with an inhibitory peptide to PKG (PKGI) increased endogenous inspiratory‐drive currents and exogenous AMPA‐induced currents. Application of 8‐Br‐cGMP with PKGI had no further effect on spontaneous or evoked currents, confirming that the observed effects were induced by PKG. However, PKG differentially increased longer‐term plasticity. Three 3 min applications (separated by 5 min) of the α 1 ‐adrenergic agonist phenylephrine (PE) in combination with 8‐Br‐cGMP yielded greater in vitro long‐term facilitation than PE alone. These data indicate the presence of a cGMP/PKG‐dependent signalling pathway in XII motoneurones that modulates inspiratory drive currents and plasticity of XII motoneurones, possibly contributing to their adaptation during physiological challenges, such as sleep and exercise.