Graduation Year

2012

Document Type

Dissertation

Degree

Ph.D.

Degree Granting Department

Medical Sciences

Major Professor

Jay B. Dean

Keywords

Anoxia, Brainstem, Hypercapnia, Hyperoxia, Hypoxia, Respiration

Abstract

This study tested the hypothesis that decreasing the control O2 level from 95% to 40% (5% CO2 + 55% N2) maintains viability in caudal solitary complex (cSC) neurons in transverse slices (~300-400ꝳ) prepared from neonatal rat (P2-22) maintained at 32-34°C. The underlying rationale is to reduce exposure to redox and nitrosative stimuli generated during several hours of exposure to 95% O2 that produces a tissue O2 tension throughout the slice which is in excess of 203 kPa (2.0 atmospheres absolute,ATA) oxygen. Whole cell recordings of cSC neurons maintained in 40% O2 exhibited spontaneous firing and had similar membrane potentials (Vm) and input resistances (Rin) as cSC neurons maintained in 95% O2. Neurons maintained in 40% O2, however, had significantly lower intrinsic firing rates than those maintained in 95% O2. 67% of neurons maintained in 40% O2 control were stimulated by hyperoxia, compared to 81% of neurons maintained in 95% O2 that were stimulated by reoxygenation from relative hypoxia. cSC neurons maintained in 40% O2 also exhibited CO2/H+-sensitivity, including CO2/H+-excitation (31%) and CO2H+-inhibition (31%) and most CO2/H+-sensitive neurons were also stimulated by hyperoxia and reoxygenation or inhibited by lower O2. It is also suggested that acute exposure to lower concentrations of O2 may increase the incidence of CO2-inhibited cSC neurons. Anoxia reduced or eliminated all firing in essentially all cSC neurons. Our findings indicate that brainstem slice viability is retained in 40% O2 control and that hyperoxia is a general stimulant of many cSC neurons, including chemosensitive neurons. We therefore recommend that 40% O2 be used for brainstem electrophysiology studies.

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