Isoflurane abolishes spontaneous firing of serotonin neurons and masks their pH/CO₂ chemosensitivity

Cory A Massey; Kimberly E Iceman; Sara L Johansen; Yuanming Wu; Michael B Harris; George B Richerson

doi:10.1152/jn.01073.2014

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Isoflurane abolishes spontaneous firing of serotonin neurons and masks their pH/CO₂ chemosensitivity

Journal article

Open access

Peer reviewed

Isoflurane abolishes spontaneous firing of serotonin neurons and masks their pH/CO₂ chemosensitivity

Cory A Massey, Kimberly E Iceman, Sara L Johansen, Yuanming Wu, Michael B Harris and George B Richerson

Journal of neurophysiology, Vol.113(7), pp.2879-2888

04/01/2015

DOI: 10.1152/jn.01073.2014

PMCID: PMC4416618

PMID: 25695656

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Abstract

Serotonin (5-hydroxytryptamine, 5-HT) neurons from the mouse and rat rostral medulla are stimulated by increased CO2 when studied in culture or brain slices. However, the response of 5-HT neurons has been variable when animals are exposed to hypercapnia in vivo. Here we examined whether halogenated inhalational anesthetics, which activate TWIK-related acid-sensitive K(+) (TASK) channels, could mask an effect of CO2 on 5-HT neurons. During in vivo plethysmography in mice, isoflurane (1%) markedly reduced the hypercapnic ventilatory response (HCVR) by 78-96% depending upon mouse strain and ambient temperature. In a perfused rat brain stem preparation, isoflurane (1%) reduced or silenced spontaneous firing of medullary 5-HT neurons in situ and abolished their responses to elevated perfusate Pco2. In dissociated cell cultures, isoflurane (1%) hyperpolarized 5-HT neurons by 6.52 ± 3.94 mV and inhibited spontaneous firing. A subsequent decrease in pH from 7.4 to 7.2 depolarized neurons by 4.07 ± 2.10 mV, but that was insufficient to reach threshold for firing. Depolarizing current restored baseline firing and the firing frequency response to acidosis, indicating that isoflurane did not block the underlying mechanisms mediating chemosensitivity. These results demonstrate that isoflurane masks 5-HT neuron chemosensitivity in vitro and in situ and markedly decreases the HCVR in vivo. The use of this class of anesthetic has a particularly potent inhibitory effect on chemosensitivity of 5-HT neurons.

Chemoreceptor Cells - drug effects

Serotonergic Neurons - physiology

Anesthetics, Inhalation - administration & dosage

Serotonergic Neurons - drug effects

Isoflurane - administration & dosage

Cells, Cultured

Rats

Serotonergic Neurons - chemistry

Carbon Dioxide - administration & dosage

Male

Chemoreceptor Cells - physiology

Rats, Sprague-Dawley

Action Potentials - physiology

Chemoreceptor Cells - chemistry

Neural Inhibition - physiology

Animals

Mice

Neural Inhibition - drug effects

Action Potentials - drug effects

Hydrogen-Ion Concentration

Details

Title: Subtitle: Isoflurane abolishes spontaneous firing of serotonin neurons and masks their pH/CO₂ chemosensitivity
Creators: Cory A Massey - Interdisciplinary Graduate Program in Neuroscience, University of Iowa Hospitals and Clinics, Iowa City, Iowa; Department of Neurology and NIH/NINDS Center for SUDEP Research, University of Iowa Hospitals and Clinics, Iowa City, Iowa; cory-massey@uiowa.edu
Kimberly E Iceman - Department of Biology and Wildlife, University of Alaska, Fairbanks, Alaska
Sara L Johansen - Department of Biology and Wildlife, University of Alaska, Fairbanks, Alaska
Yuanming Wu - Department of Neurology and NIH/NINDS Center for SUDEP Research, University of Iowa Hospitals and Clinics, Iowa City, Iowa
Michael B Harris - Department of Biology and Wildlife, University of Alaska, Fairbanks, Alaska; Institute of Arctic Biology, University of Alaska, Fairbanks, Alaska
George B Richerson - Department of Neurology and NIH/NINDS Center for SUDEP Research, University of Iowa Hospitals and Clinics, Iowa City, Iowa; Department of Molecular Physiology and Biophysics, University of Iowa Hospitals and Clinics, Iowa City, Iowa; and Department of Veterans Affairs Medical Center, Iowa City, Iowa
Resource Type: Journal article
Publication Details: Journal of neurophysiology, Vol.113(7), pp.2879-2888
DOI: 10.1152/jn.01073.2014
PMID: 25695656
PMCID: PMC4416618
NLM abbreviation: J Neurophysiol
ISSN: 0022-3077
eISSN: 1522-1598
Publisher: United States
Grant note: R01 HD-052772 / NICHD NIH HHS 2U54 NS-041069 / NINDS NIH HHS P20 GM-103395 / NIGMS NIH HHS P20 NS-076916 / NINDS NIH HHS P01 HD-36379 / NICHD NIH HHS U01 NS090414 / NINDS NIH HHS
Language: English
Date published: 04/01/2015
Academic Unit: Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Neurosurgery
Record Identifier: 9984020764102771

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