Chronic intermittent hypoxia alters NMDA and AMPA-evoked currents in NTS neurons receiving carotid body chemoreceptor inputs.
Chronic exposure to intermittent hypoxia (CIH) has been used in animals to mimic the arterial hypoxemia that accompanies sleep apnea. Humans with sleep apnea and animals exposed to CIH have elevated blood pressures and augmented sympathetic nervous system responses to acute exposures to hypoxia. To test the hypothesis that exposure to CIH alters neurons within the nucleus of the solitary tract (NTS) that integrate arterial chemoreceptor afferent inputs, we measured whole cell currents induced by activation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and N-methyl-D-aspartate (NMDA) receptors in enzymatically dispersed NTS neurons from normoxic (NORM) and CIH-exposed rats (alternating cycles of 3 min at 10% O2 followed by 3 min at 21% O2 between 8 AM and 4 PM for 7 days). To identify NTS neurons receiving carotid body afferent inputs the anterograde tracer 4- (4-(dihexadecylamino)styryl-N-methylpyridinum iodide (DiA) was placed onto the carotid body 1 wk before exposure to CIH. AMPA dose-response curves had similar EC50 but maximal responses increased in neurons isolated from DiA-labeled CIH (20.1 +/- 0.8 microM, n = 9) compared with NORM (6.0 +/- 0.3 microM, n = 8) rats. NMDA dose-response curves also had similar EC50 but maximal responses decreased in CIH (8.4 +/- 0.4 microM, n = 8) compared with NORM (19.4 +/- 0.6 microM, n = 9) rats. These results suggest reciprocal changes in the number and/or conductance characteristics of AMPA and NMDA receptors. Enhanced responses to AMPA receptor activation could contribute to enhanced chemoreflex responses observed in animals exposed to CIH and humans with sleep apnea.
de Paula
Patricia M
PM
Department of Pharmacology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900, USA. mifflin@uthscsa.edu
Tolstykh
Gleb
G
Mifflin
Steve
S
D000344:Afferent Pathways / Q000187:drug effects / Q000503:physiopathology; D000818:Animals; D002344:Carotid Body / Q000187:drug effects / Q000503:physiopathology*; D002478:Cells, Cultured; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects*; D008297:Male; D016202:N-Methylaspartate / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017552:Solitary Nucleus / Q000187:drug effects / Q000503:physiopathology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000008:administration & dosage*
D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid