Possible role of GABAergic depolarization in neocortical neurons in generating hyperexcitatory behaviors during emergence from sevoflurane anesthesia in the rat

Byung Gun Lim, Feng Yan Shen, Young Beom Kim, Woong Bin Kim, Yoon Sik Kim, Hee Chul Han, Mi Kyoung Lee, Myounghoon Kong, Yang In Kim

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Hyperexcitatory behaviors occurring after sevoflurane anesthesia are of serious clinical concern, but the underlying mechanism is unknown. These behaviors may result from the potentiation by sevoflurane of GABAergic depolarization/excitation in neocortical neurons, cells implicated in the genesis of consciousness and arousal. The current study sought to provide evidence for this hypothesis with rats, the neocortical neurons of which are known to respond to GABA (γ-aminobutyric acid) with depolarization/excitation at early stages of development (i.e., until the second postnatal week) and with hyperpolarization/inhibition during adulthood. Employing behavioral tests and electrophysiological recordings in neocortical slice preparations, we found: (1) sevoflurane produced PAHBs (post-anesthetic hyperexcitatory behaviors) in postnatal day (P)1-15 rats, whereas it failed to elicit PAHBs in P16 or older rats; (2) GABAergic PSPs (postsynaptic potentials) were depolarizing/excitatory in the neocortical neurons of P5 and P10 rats, whereas mostly hyperpolarizing/inhibitory in the cells of adult rats; (3) at P14-15, 50% of rats had PAHBs and, in general, the cells of the animals with PAHBs exhibited strongly depolarizing GABAergic PSPs, whereas those without PAHBs showed hyperpolarizing or weakly depolarizing GABAergic PSPs; (4) bumetanide [inhibitor of the Cl - importer NKCC (Na + -K + -2Cl - cotransporter)] treatment at P5 suppressed PAHBs and depolarizing GABAergic responses; and (5) sevoflurane at 1% (i.e., concentration 1 minimum alveolar concentration) potentiated depolarizing GABAergic PSPs in the neurons of P5 and P10 rats and of P14-15 animals with PAHBs, evoking action potentials in ≥50% of these cells. On the basis of these results, we conclude that sevoflurane may produce PAHBs by potentiating GABAergic depolarization/excitation in neocortical neurons.

Original languageEnglish
Article numbere00141
Pages (from-to)127-136
Number of pages10
JournalASN Neuro
Volume6
Issue number2
DOIs
Publication statusPublished - 2014 Jan 1

Fingerprint

Anesthesia
Anesthetics
Neurons
Synaptic Potentials
sevoflurane
Aminobutyrates
Bumetanide
Arousal
Consciousness
gamma-Aminobutyric Acid
Action Potentials

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

Cite this

Possible role of GABAergic depolarization in neocortical neurons in generating hyperexcitatory behaviors during emergence from sevoflurane anesthesia in the rat. / Lim, Byung Gun; Shen, Feng Yan; Kim, Young Beom; Kim, Woong Bin; Kim, Yoon Sik; Han, Hee Chul; Lee, Mi Kyoung; Kong, Myounghoon; Kim, Yang In.

In: ASN Neuro, Vol. 6, No. 2, e00141, 01.01.2014, p. 127-136.

Research output: Contribution to journalArticle

@article{e14b7ba5735c46cb88eb0478134a8aaf,
title = "Possible role of GABAergic depolarization in neocortical neurons in generating hyperexcitatory behaviors during emergence from sevoflurane anesthesia in the rat",
abstract = "Hyperexcitatory behaviors occurring after sevoflurane anesthesia are of serious clinical concern, but the underlying mechanism is unknown. These behaviors may result from the potentiation by sevoflurane of GABAergic depolarization/excitation in neocortical neurons, cells implicated in the genesis of consciousness and arousal. The current study sought to provide evidence for this hypothesis with rats, the neocortical neurons of which are known to respond to GABA (γ-aminobutyric acid) with depolarization/excitation at early stages of development (i.e., until the second postnatal week) and with hyperpolarization/inhibition during adulthood. Employing behavioral tests and electrophysiological recordings in neocortical slice preparations, we found: (1) sevoflurane produced PAHBs (post-anesthetic hyperexcitatory behaviors) in postnatal day (P)1-15 rats, whereas it failed to elicit PAHBs in P16 or older rats; (2) GABAergic PSPs (postsynaptic potentials) were depolarizing/excitatory in the neocortical neurons of P5 and P10 rats, whereas mostly hyperpolarizing/inhibitory in the cells of adult rats; (3) at P14-15, 50{\%} of rats had PAHBs and, in general, the cells of the animals with PAHBs exhibited strongly depolarizing GABAergic PSPs, whereas those without PAHBs showed hyperpolarizing or weakly depolarizing GABAergic PSPs; (4) bumetanide [inhibitor of the Cl - importer NKCC (Na + -K + -2Cl - cotransporter)] treatment at P5 suppressed PAHBs and depolarizing GABAergic responses; and (5) sevoflurane at 1{\%} (i.e., concentration 1 minimum alveolar concentration) potentiated depolarizing GABAergic PSPs in the neurons of P5 and P10 rats and of P14-15 animals with PAHBs, evoking action potentials in ≥50{\%} of these cells. On the basis of these results, we conclude that sevoflurane may produce PAHBs by potentiating GABAergic depolarization/excitation in neocortical neurons.",
keywords = "Emergence agitation, GABA, KCC2, Neocortex, NKCC1, Sevoflurane",
author = "Lim, {Byung Gun} and Shen, {Feng Yan} and Kim, {Young Beom} and Kim, {Woong Bin} and Kim, {Yoon Sik} and Han, {Hee Chul} and Lee, {Mi Kyoung} and Myounghoon Kong and Kim, {Yang In}",
year = "2014",
month = "1",
day = "1",
doi = "10.1042/AN20140004",
language = "English",
volume = "6",
pages = "127--136",
journal = "ASN Neuro",
issn = "1759-0914",
publisher = "Portland Press Ltd.",
number = "2",

}

TY - JOUR

T1 - Possible role of GABAergic depolarization in neocortical neurons in generating hyperexcitatory behaviors during emergence from sevoflurane anesthesia in the rat

AU - Lim, Byung Gun

AU - Shen, Feng Yan

AU - Kim, Young Beom

AU - Kim, Woong Bin

AU - Kim, Yoon Sik

AU - Han, Hee Chul

AU - Lee, Mi Kyoung

AU - Kong, Myounghoon

AU - Kim, Yang In

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Hyperexcitatory behaviors occurring after sevoflurane anesthesia are of serious clinical concern, but the underlying mechanism is unknown. These behaviors may result from the potentiation by sevoflurane of GABAergic depolarization/excitation in neocortical neurons, cells implicated in the genesis of consciousness and arousal. The current study sought to provide evidence for this hypothesis with rats, the neocortical neurons of which are known to respond to GABA (γ-aminobutyric acid) with depolarization/excitation at early stages of development (i.e., until the second postnatal week) and with hyperpolarization/inhibition during adulthood. Employing behavioral tests and electrophysiological recordings in neocortical slice preparations, we found: (1) sevoflurane produced PAHBs (post-anesthetic hyperexcitatory behaviors) in postnatal day (P)1-15 rats, whereas it failed to elicit PAHBs in P16 or older rats; (2) GABAergic PSPs (postsynaptic potentials) were depolarizing/excitatory in the neocortical neurons of P5 and P10 rats, whereas mostly hyperpolarizing/inhibitory in the cells of adult rats; (3) at P14-15, 50% of rats had PAHBs and, in general, the cells of the animals with PAHBs exhibited strongly depolarizing GABAergic PSPs, whereas those without PAHBs showed hyperpolarizing or weakly depolarizing GABAergic PSPs; (4) bumetanide [inhibitor of the Cl - importer NKCC (Na + -K + -2Cl - cotransporter)] treatment at P5 suppressed PAHBs and depolarizing GABAergic responses; and (5) sevoflurane at 1% (i.e., concentration 1 minimum alveolar concentration) potentiated depolarizing GABAergic PSPs in the neurons of P5 and P10 rats and of P14-15 animals with PAHBs, evoking action potentials in ≥50% of these cells. On the basis of these results, we conclude that sevoflurane may produce PAHBs by potentiating GABAergic depolarization/excitation in neocortical neurons.

AB - Hyperexcitatory behaviors occurring after sevoflurane anesthesia are of serious clinical concern, but the underlying mechanism is unknown. These behaviors may result from the potentiation by sevoflurane of GABAergic depolarization/excitation in neocortical neurons, cells implicated in the genesis of consciousness and arousal. The current study sought to provide evidence for this hypothesis with rats, the neocortical neurons of which are known to respond to GABA (γ-aminobutyric acid) with depolarization/excitation at early stages of development (i.e., until the second postnatal week) and with hyperpolarization/inhibition during adulthood. Employing behavioral tests and electrophysiological recordings in neocortical slice preparations, we found: (1) sevoflurane produced PAHBs (post-anesthetic hyperexcitatory behaviors) in postnatal day (P)1-15 rats, whereas it failed to elicit PAHBs in P16 or older rats; (2) GABAergic PSPs (postsynaptic potentials) were depolarizing/excitatory in the neocortical neurons of P5 and P10 rats, whereas mostly hyperpolarizing/inhibitory in the cells of adult rats; (3) at P14-15, 50% of rats had PAHBs and, in general, the cells of the animals with PAHBs exhibited strongly depolarizing GABAergic PSPs, whereas those without PAHBs showed hyperpolarizing or weakly depolarizing GABAergic PSPs; (4) bumetanide [inhibitor of the Cl - importer NKCC (Na + -K + -2Cl - cotransporter)] treatment at P5 suppressed PAHBs and depolarizing GABAergic responses; and (5) sevoflurane at 1% (i.e., concentration 1 minimum alveolar concentration) potentiated depolarizing GABAergic PSPs in the neurons of P5 and P10 rats and of P14-15 animals with PAHBs, evoking action potentials in ≥50% of these cells. On the basis of these results, we conclude that sevoflurane may produce PAHBs by potentiating GABAergic depolarization/excitation in neocortical neurons.

KW - Emergence agitation

KW - GABA

KW - KCC2

KW - Neocortex

KW - NKCC1

KW - Sevoflurane

UR - http://www.scopus.com/inward/record.url?scp=84901920964&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84901920964&partnerID=8YFLogxK

U2 - 10.1042/AN20140004

DO - 10.1042/AN20140004

M3 - Article

VL - 6

SP - 127

EP - 136

JO - ASN Neuro

JF - ASN Neuro

SN - 1759-0914

IS - 2

M1 - e00141

ER -