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

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  • Author(s): Saywell SA;Saywell SA; Babiec WE; Neverova NV; Feldman JL
  • Source:
    The Journal of physiology [J Physiol] 2010 Nov 15; Vol. 588 (Pt 22), pp. 4431-9. Date of Electronic Publication: 2010 Sep 20.
  • Publication Type:
    Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Cambridge Univ. Press Country of Publication: England NLM ID: 0266262 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1469-7793 (Electronic) Linking ISSN: 00223751 NLM ISO Abbreviation: J Physiol Subsets: MEDLINE
    • Publication Information:
      Publication: Oxford : Blackwell : Cambridge Univ. Press
      Original Publication: London, Cambridge Univ. Press.
    • Subject Terms:
      Cyclic GMP-Dependent Protein Kinases/*physiology ; Hypoglossal Nerve/*enzymology ; Long-Term Potentiation/*physiology ; Motor Neurons/*enzymology; 8-Bromo Cyclic Adenosine Monophosphate/pharmacology ; Animals ; Animals, Newborn ; Hypoglossal Nerve/drug effects ; Inhalation/drug effects ; Inhalation/physiology ; Long-Term Potentiation/drug effects ; Motor Neurons/drug effects ; Rats ; Rats, Sprague-Dawley
    • Abstract:
      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.
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    • Grant Information:
      R01 NS024742 United States NS NINDS NIH HHS; T32 NS058280 United States NS NINDS NIH HHS; F31 NS067933 United States NS NINDS NIH HHS; NS067933 United States NS NINDS NIH HHS; NS24742 United States NS NINDS NIH HHS
    • Accession Number:
      23583-48-4 (8-Bromo Cyclic Adenosine Monophosphate)
      EC 2.7.11.12 (Cyclic GMP-Dependent Protein Kinases)
    • Publication Date:
      Date Created: 20100922 Date Completed: 20110930 Latest Revision: 20211020
    • Publication Date:
      20221213
    • Accession Number:
      PMC3008849
    • Accession Number:
      10.1113/jphysiol.2010.194209
    • Accession Number:
      20855434