Changes in glutamate receptor subunits within the medulla in goats after section of the carotid sinus nerves.
The mechanisms which contribute to the time-dependent recovery of resting ventilation and the ventilatory CO2 chemoreflex after carotid body denervation (CBD) are poorly understood. Herein we tested the hypothesis that there are time-dependent changes in the expression of specific AMPA, NMDA, and/or neurokinin-1 (NK1R) receptors within respiratory-related brain stem nuclei acutely or chronically after CBD in adult goats. Brain stem tissues were collected acutely (5 days) or chronically (30 days) after sham or bilateral CBD, immunostained with antibodies targeting AMPA (GluA1 or GluA2), NMDA (GluN1), or NK-1 receptors, and optical density (OD) compared. Physiological measurement confirmed categorization of each group and showed ventilatory effects consistent with bilateral CBD (Miller et al. J Appl Physiol 115: 1088-1098, 2013). Acutely after CBD, GluA1 OD was unchanged or slightly increased, but GluA2 and GluN1 OD were reduced 15-30% within the nucleus tractus solitarius (NTS) and in other medullary respiratory nuclei. Chronically after CBD, GluA1 was reduced (P < 0.05) within the caudal NTS and in other nuclei, but there was significant recovery of GluA2 and GluN1 OD. NK1 OD was not significantly different from control after CBD. We conclude that the initial decrease in GluA2 and GluN1 after CBD likely contributes to hypoventilation and the reduced CO2 chemoreflex. The partial recovery of ventilation and the CO2 chemoreflex after CBD parallel a time-dependent return of these receptors to near control levels but likely depend upon additional initiating and maintenance factors for neuroplasticity.
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin;
Justin Robert
JR
Miller
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin;
Suzanne
S
Neumueller
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin;
Clarissa
C
Muere
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin;
Samantha
S
Olesiak
Department of Physical Therapy, Marquette University, Milwaukee, Wisconsin;
Lawrence
L
Pan
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin;
John D
JD
Bukowy
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin;
Asem O
AO
Daghistany
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin; Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin; and.
Matthew R
MR
Hodges
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin; Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin; and Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin.
Hubert V
HV
Forster
D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D002344:Carotid Body / Q000378:metabolism*; D002346:Carotid Sinus / Q000378:metabolism*; D003714:Denervation / Q000379:methods; D005260:Female; D006041:Goats / Q000378:metabolism*; D008526:Medulla Oblongata / Q000378:metabolism*; D016202:N-Methylaspartate / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism*; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D012119:Respiration; D017552:Solitary Nucleus / Q000378:metabolism
D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018040:Receptors, Neurokinin-1; D002245:Carbon Dioxide; D016202:N-Methylaspartate
carotid body; neurochemical receptor; plasticity