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Departments of 1 Pediatrics and 3 Physiology and 4 Interdepartmental Neuroscience Program, Constance S. Kaufman Pediatric Pulmonary Research Laboratory, Tulane University School of Medicine, New Orleans, Louisiana 70112; and 2 Department of Physical Therapy, Exercise and Nutrition Sciences, State University of New York at Buffalo, Buffalo, New York 14214
The developmental role of
-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) glutamate
receptors in respiratory regulation remains undefined. To
study this issue, minute ventilation
(
E) was measured in 5-, 10-, and
15-day-old intact freely behaving rat pups using whole body
plethysmography during room air (RA), hypercapnic (5%
CO2), and hypoxic (10% O2) conditions, both
before and after administration of the
non-N-methyl-D-aspartate (NMDA) receptor antagonist
1,2,3,4-tetrahydro-6-nitro-2,3-dioxobenzo[f]quinoxaline-7-sulfonamide disodium (NBQX; 10 mg/kg ip). In all age groups,
E during RA was unaffected by
NBQX, despite reductions in breathing frequency (f)
induced by increases in both inspiratory and expiratory duration. During hypoxia and hypercapnia, E
increases were similar in both NBQX and control conditions in all age
groups. However, tidal volume was greater and f lower after
NBQX. To determine if AMPA receptor-positive neurons are recruited
during hypoxia, immunostaining for AMPA receptor (GluR2/3) and
c-fos colabeling was performed in caudal brain stem
sections after exposing rat pups at postnatal ages 2, 5, 10, and 20 days, and adult rats to room air or 10% O2 for 3 h. GluR2/3 expression increased with postnatal age in the nucleus of
the solitary tract (NTS) and hypoglossal nucleus, whereas
a biphasic pattern emerged for the nucleus ambiguus (NA). c-fos expression was enhanced by hypoxia at all
postnatal ages in the NTS and NA and also demonstrated a clear
maturational pattern. However, colocalization of GluR2/3
and c-fos was not affected by hypoxia. We
conclude that AMPA glutamate receptor expression in the caudal brain
stem is developmentally regulated. Furthermore, the role of non-NMDA
receptors in respiratory control of conscious neonatal rats appears to
be limited to modest, albeit significant, regulation of breathing pattern.
hypoxia; hypercapnia; normoxia; nucleus of the solitary tract; caudal brain stem
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