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Volume 17, Number 16,
Issue of August 15, 1997
pp. 6325-6337
Copyright ©1997 Society for Neuroscience
P2 Receptor Excitation of Rodent Hypoglossal Motoneuron Activity
In Vitro and In Vivo: A Molecular Physiological
Analysis
Received Jan. 22, 1997; revised May 2, 1997; accepted May 9, 1997.
Gregory D. Funk,
Refik Kanjhan,
Carmen Walsh,
Janusz Lipski,
Alison M. Comer,
Marjorie A. Parkis, and
Gary D. Housley
Department of Physiology, Faculty of Medicine and Health Science,
University of Auckland, Auckland, New Zealand
The role of P2 receptors in controlling hypoglossal motoneuron (XII
MN) output was examined (1) electrophysiologically, via application of
ATP to the hypoglossal nucleus of rhythmically active mouse medullary
slices and anesthetized adult rats; (2) immunohistochemically, using an
antiserum against the P2X2 receptor subunit; and (3) using
PCR to identify expression of P2X2 receptor subunits in
micropunches of tissue taken from the XII motor nucleus. Application of
ATP to the hypoglossal nucleus of mouse medullary slices and
anesthetized rats produced a suramin-sensitive excitation of
hypoglossal nerve activity. Additional in vitro effects
included potentiation of inspiratory hypoglossal nerve output via a
suramin- and pyridoxal-phosphate-6-azophenyl-2 ,4 -disulphonic
acid (PPADS)-sensitive mechanism, XII MN depolarization via activation
of a suramin-sensitive inward current, decreased neuronal input
resistance, and a slow-onset theophylline-sensitive reduction of
inspiratory output likely resulting from hydrolysis of extracellular
ATP to adenosine and activation of P1 receptors. Immunohistochemically,
P2X2 receptors were detected in inspiratory XII MNs that
were labeled with Lucifer yellow. These data, combined with
identification of mRNA for three P2X2 receptor subunit
isoforms within the hypoglossal nucleus (two of which have not been
localized previously in brain) and the previous demonstration that P2X
receptors are ubiquitously expressed in cranial and spinal motoneuron
pools, support not only a role of P2 receptors in modulating
inspiratory hypoglossal activity but a general role of P2 receptors in
modulating motor outflow from the CNS.
Key words:
respiration;
P2 receptor;
hypoglossal motoneuron;
ATP;
suramin;
PPADS;
adenosine;
medullary brain slice;
rat;
mouse
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