Daily Isoflurane Exposure Increases Barbiturate Insensitivity in Medullary Respiratory and Cortical Neurons via Expression of ε-Subunit Containing GABA ARs

By March 6, 2015

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Keith B. Hengen Mary Behan
PLoS ONE Slice Rat Cortex in vitro Electrode A4x4-3mm-100-125-177

The parameters governing GABAA receptor subtype expression patterns are not well understood,
although significant shifts in subunit expression may support key physiological
events. For example, the respiratory control network in pregnant rats becomes relatively insensitive
to barbiturates due to increased expression of ε-subunit-containing GABAARs in
the ventral respiratory column. We hypothesized that this plasticity may be a compensatory
response to a chronic increase in inhibitory tone caused by increased central neurosteroid
levels. Thus, we tested whether increased inhibitory tone was sufficient to induce ε-subunit
upregulation on respiratory and cortical neurons in adult rats. Chronic intermittent increases
in inhibitory tone in male and female rats was induced via daily 5-min exposures to 3% isoflurane.
After 7d of treatment, phrenic burst frequency was less sensitive to barbiturate in
isoflurane-treated male and female rats in vivo. Neurons in the ventral respiratory group and
cortex were less sensitive to pentobarbital in vitro following 7d and 30d of intermittent isoflurane-
exposure in both male and female rats. The pentobarbital insensitivity in 7d isoflurane-
treated rats was reversible after another 7d. We hypothesize that increased inhibitory
tone in the respiratory control network and cortex causes a compensatory increase in ε-subunit-
containing GABAARs.

Published online 2015 Mar 6. doi: 10.1371/journal.pone.0119351

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4352015/ March 6, 2015 University of Wisconsin