Protein kinase G-dependent mechanisms modulate hypoglossal motoneuronal excitability and long-term facilitation. 2010

Shane A Saywell, and Walter E Babiec, and Natalia V Neverova, and Jack L Feldman
Department of Neurobiology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Box 951763, Los Angeles, CA 90095-1763, USA.

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.

UI MeSH Term Description Entries
D007002 Hypoglossal Nerve The 12th cranial nerve. The hypoglossal nerve originates in the hypoglossal nucleus of the medulla and supplies motor innervation to all of the muscles of the tongue except the palatoglossus (which is supplied by the vagus). This nerve also contains proprioceptive afferents from the tongue muscles. Cranial Nerve XII,Twelfth Cranial Nerve,Nerve XII,Nervus Hypoglossus,Cranial Nerve XIIs,Cranial Nerve, Twelfth,Cranial Nerves, Twelfth,Hypoglossal Nerves,Hypoglossus, Nervus,Nerve XII, Cranial,Nerve XIIs,Nerve XIIs, Cranial,Nerve, Hypoglossal,Nerve, Twelfth Cranial,Nerves, Hypoglossal,Nerves, Twelfth Cranial,Twelfth Cranial Nerves,XII, Nerve,XIIs, Nerve
D009046 Motor Neurons Neurons which activate MUSCLE CELLS. Neurons, Motor,Alpha Motorneurons,Motoneurons,Motor Neurons, Alpha,Neurons, Alpha Motor,Alpha Motor Neuron,Alpha Motor Neurons,Alpha Motorneuron,Motoneuron,Motor Neuron,Motor Neuron, Alpha,Motorneuron, Alpha,Motorneurons, Alpha,Neuron, Alpha Motor,Neuron, Motor
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000831 Animals, Newborn Refers to animals in the period of time just after birth. Animals, Neonatal,Animal, Neonatal,Animal, Newborn,Neonatal Animal,Neonatal Animals,Newborn Animal,Newborn Animals
D001239 Inhalation The act of BREATHING in. Inhaling,Inspiration, Respiratory,Respiratory Inspiration
D015124 8-Bromo Cyclic Adenosine Monophosphate A long-acting derivative of cyclic AMP. It is an activator of cyclic AMP-dependent protein kinase, but resistant to degradation by cyclic AMP phosphodiesterase. 8-Bromo-cAMP,8-Br Cyclic AMP,8-Bromo Cyclic AMP,8-Bromo Cyclic Adenosine Monophosphate, Monosodium Salt,8-Bromo Cyclic Adenosine Monophosphate, Sodium Salt,8-Bromoadenosine 3',5'-Cyclic Monophosphate,Br Cycl AMP,8 Br Cyclic AMP,8 Bromo Cyclic AMP,8 Bromo Cyclic Adenosine Monophosphate,8 Bromo Cyclic Adenosine Monophosphate, Monosodium Salt,8 Bromo Cyclic Adenosine Monophosphate, Sodium Salt,8 Bromo cAMP,8 Bromoadenosine 3',5' Cyclic Monophosphate,AMP, Br Cycl,Cyclic AMP, 8-Br,Cyclic AMP, 8-Bromo
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D017774 Long-Term Potentiation A persistent increase in synaptic efficacy, usually induced by appropriate activation of the same synapses. The phenomenological properties of long-term potentiation suggest that it may be a cellular mechanism of learning and memory. Long Term Potentiation,Long-Term Potentiations,Potentiation, Long-Term,Potentiations, Long-Term
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D017869 Cyclic GMP-Dependent Protein Kinases A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins. Guanosine Cyclic Monophosphate-Dependent Protein Kinase,Guanosine Cyclic Monophosphate-Dependent Protein Kinases,cGMP-Dependent Protein Kinase,cGMP-Dependent Protein Kinases,Cyclic GMP-Dependent Protein Kinase,G-Kinase,G-Kinases,Guanosine Cyclic 3',5'-Phosphate-Dependent Protein Kinase,Protein Kinase G,Cyclic GMP Dependent Protein Kinase,Cyclic GMP Dependent Protein Kinases,G Kinase,G Kinases,Guanosine Cyclic 3',5' Phosphate Dependent Protein Kinase,Guanosine Cyclic Monophosphate Dependent Protein Kinase,Guanosine Cyclic Monophosphate Dependent Protein Kinases,Kinase, cGMP-Dependent Protein,Kinases, cGMP-Dependent Protein,Protein Kinase, cGMP-Dependent,Protein Kinases, cGMP-Dependent,cGMP Dependent Protein Kinase,cGMP Dependent Protein Kinases

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