Hengen Keith B, Nelson Nathan R, Stang Kyle M, Johnson Stephen M, Smith Stephanie M, Watters Jyoti J, Mitchell Gordon S, Behan Mary
Neuroscience Training Program, University of Wisconsin, Madison, Madison, Wisconsin, United States of America.
Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, Madison, Wisconsin, United States of America.
PLoS One. 2015 Mar 6;10(3):e0119351. doi: 10.1371/journal.pone.0119351. eCollection 2015.
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.
尽管亚基表达的显著变化可能支持关键的生理事件，但控制GABAA受体亚型表达模式的参数尚未得到很好的理解。例如，由于腹侧呼吸柱中含ε亚基的GABAARs表达增加，怀孕大鼠的呼吸控制网络对巴比妥类药物变得相对不敏感。我们假设这种可塑性可能是对中枢神经甾体水平升高导致的抑制性张力慢性增加的一种代偿反应。因此，我们测试了增加的抑制性张力是否足以诱导成年大鼠呼吸和皮质神经元上的ε亚基上调。通过每天5分钟暴露于3%异氟醚来诱导雄性和雌性大鼠的抑制性张力慢性间歇性增加。治疗7天后，在体内，异氟醚处理的雄性和雌性大鼠的膈神经爆发频率对巴比妥类药物的敏感性降低。在雄性和雌性大鼠中，间歇性异氟醚暴露7天和30天后，腹侧呼吸组和皮质中的神经元在体外对戊巴比妥的敏感性降低。在7天异氟醚处理的大鼠中，戊巴比妥不敏感性在再过7天后是可逆的。我们假设呼吸控制网络和皮质中增加的抑制性张力会导致含ε亚基的GABAARs代偿性增加。
