S L Johansen1, K E Iceman1, C R Iceman2, B E Taylor1, M B Harris3. 1. Institute of Arctic Biology, Department of Biology and Wildlife, University of Alaska, Fairbanks, AK 99775, USA. 2. Department of Chemistry and Biochemistry, University of Alaska, Fairbanks, AK 99775, USA. 3. Institute of Arctic Biology, Department of Biology and Wildlife, University of Alaska, Fairbanks, AK 99775, USA. Electronic address: mbharris@alaska.edu.
Abstract
BACKGROUND: Anesthetics have a profound influence on a myriad of autonomic processes. Mechanisms of general anesthesia, and how these mechanisms give rise to the multifaceted state of anesthesia, are largely unknown. The ascending and descending serotonin (5-HT) networks are key modulators of autonomic pathways, and are critically involved in homeostatic reflexes across the motor, somatosensory, limbic and autonomic systems. These 5-HT networks are thought to contribute to anesthetic effects, but how anesthetics affect 5-HT neuron function remains a pertinent question. We hypothesized that the volatile anesthetic isoflurane inhibits action potential discharge of medullary raphé 5-HT neurons. METHODS: We conducted extracellular recordings on individual neurons in the medullary raphé region of the unanesthetized in situ perfused brainstem preparation to determine how exposure to isoflurane affects 5-HT neurons. We examined changes in 5-HT neuron baseline firing in response to treatment with either 1, 1.5, or 2% isoflurane. We measured isoflurane concentrations by gas chromatography-mass spectrometry (GC-MS) analysis. RESULTS: Exposure to isoflurane inhibited action potential discharge in raphé 5-HT neurons. We document a concentration-dependent inhibition over a range of concentrations approximating isoflurane MAC (minimum alveolar concentration required for surgical anesthesia). Delivered concentrations of isoflurane were confirmed using GC-MS analysis. CONCLUSIONS: These findings illustrate that halogenated anesthetics greatly affect 5-HT neuron firing and suggest 5-HT neuron contributions to mechanisms of general anesthesia.
BACKGROUND: Anesthetics have a profound influence on a myriad of autonomic processes. Mechanisms of general anesthesia, and how these mechanisms give rise to the multifaceted state of anesthesia, are largely unknown. The ascending and descending serotonin (5-HT) networks are key modulators of autonomic pathways, and are critically involved in homeostatic reflexes across the motor, somatosensory, limbic and autonomic systems. These 5-HT networks are thought to contribute to anesthetic effects, but how anesthetics affect 5-HT neuron function remains a pertinent question. We hypothesized that the volatile anesthetic isoflurane inhibits action potential discharge of medullary raphé 5-HT neurons. METHODS: We conducted extracellular recordings on individual neurons in the medullary raphé region of the unanesthetized in situ perfused brainstem preparation to determine how exposure to isoflurane affects 5-HT neurons. We examined changes in 5-HT neuron baseline firing in response to treatment with either 1, 1.5, or 2% isoflurane. We measured isoflurane concentrations by gas chromatography-mass spectrometry (GC-MS) analysis. RESULTS: Exposure to isoflurane inhibited action potential discharge in raphé 5-HT neurons. We document a concentration-dependent inhibition over a range of concentrations approximating isoflurane MAC (minimum alveolar concentration required for surgical anesthesia). Delivered concentrations of isoflurane were confirmed using GC-MS analysis. CONCLUSIONS: These findings illustrate that halogenated anesthetics greatly affect 5-HT neuron firing and suggest 5-HT neuron contributions to mechanisms of general anesthesia.