• The anesthetic isoflurane influences baseline firing and disrupts chemosensitivity of 5-HT and GABA raphe neurons

      Johansen, Sara L.; Harris, Michael; Taylor, Barbara; Duffy, Larry (2014-05)
      General anesthetics are widely used in clinical and scientific contexts, but their molecular mechanisms, and how these mechanisms give rise to the state of anesthesia, are poorly understood. We investigated the influence of the volatile anesthetic isoflurane on serotonin (5-hydroxytryptamine; 5-HT) and γ-aminobutyric acid (GABA) synthesizing raphé neurons. These cell types have been proposed as central chemoreceptors, cells that sense changes in arterial CO₂/pH and stimulate respiratory output to regain homeostasis. We tested the hypotheses that isoflurane inhibits 5-HT neuron baseline firing, enhances GABA neuron baseline firing, and disrupts the chemosensitivity of both neuron types. We performed extracellular recordings in the medullary raphé using the unanesthetized in situ perfused brainstem preparation. Subsets of neurons were labeled with biotinamide using the juxtacellular labeling method and immunohistochemically identified by neurotransmitter phenotype. Results indicated that isoflurane inhibited action potential discharge in 5-HT neurons. Isoflurane inhibited action potential discharge in a subset of CO₂-inhibited putative GABA neurons and enhanced action potential discharge in a different subset of these neurons. Isoflurane disrupted the chemosensitivity of both 5-HT and GABA neurons. Disruption of 5-HT and GABA neuron chemosensitivity by isoflurane may contribute to the blunted hypercapnic ventilatory response that is a secondary effect of general anesthesia.