Anesthetic Activation of Central Respiratory Chemoreceptor Neurons Involves Inhibition of a THIK-1-Like Background K(+) Current


Autoria(s): LAZARENKO, Roman M.; FORTUNA, Michal G.; SHI, Yingtang; MULKEY, Daniel K.; TAKAKURA, Ana C.; MOREIRA, Thiago S.; GUYENET, Patrice G.; BAYLISS, Douglas A.
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

20/10/2012

20/10/2012

2010

Resumo

At surgical depths of anesthesia, inhalational anesthetics cause a loss of motor response to painful stimuli (i.e., immobilization) that is characterized by profound inhibition of spinal motor circuits. Yet, although clearly depressed, the respiratory motor system continues to provide adequate ventilation under these same conditions. Here, we show that isoflurane causes robust activation of CO(2)/pH-sensitive, Phox2b-expressing neurons located in the retrotrapezoid nucleus (RTN) of the rodent brainstem, in vitro and in vivo. In brainstem slices from Phox2b-eGFP mice, the firing of pH-sensitive RTN neurons was strongly increased by isoflurane, independent of prevailing pH conditions. At least two ionic mechanisms contributed to anesthetic activation of RTN neurons: activation of an Na(+)-dependent cationic current and inhibition of a background K(+) current. Single-cell reverse transcription-PCR analysis of dissociated green fluorescent protein-labeled RTN neurons revealed expression of THIK-1 (TWIK-related halothane-inhibited K(+) channel, K(2P)13.1), a channel that shares key properties with the native RTN current (i.e., suppression by inhalational anesthetics, weak rectification, inhibition by extracellular Na(+), and pH-insensitivity). Isoflurane also increased firing rate of RTN chemosensitive neurons in urethane-anesthetized rats, again independent of CO(2) levels. In these animals, isoflurane transiently enhanced activity of the respiratory system, an effect that was most prominent at low levels of respiratory drive and mediated primarily by an increase in respiratory frequency. These data indicate that inhalational anesthetics cause activation of RTN neurons, which serve an important integrative role in respiratory control; the increased drive provided by enhanced RTN neuronal activity may contribute, in part, to maintaining respiratory motor activity under immobilizing anesthetic conditions.

National Institutes of Health (NIH)[HL74011]

U.S. National Institutes of Health (NIH)

U.S. National Institutes of Health (NIH)

National Institutes of Health (NIH)[GM66181]

Identificador

JOURNAL OF NEUROSCIENCE, v.30, n.27, p.9324-9334, 2010

0270-6474

http://producao.usp.br/handle/BDPI/28021

10.1523/JNEUROSCI.1956-10.2010

http://dx.doi.org/10.1523/JNEUROSCI.1956-10.2010

Idioma(s)

eng

Publicador

SOC NEUROSCIENCE

Relação

Journal of Neuroscience

Direitos

restrictedAccess

Copyright SOC NEUROSCIENCE

Palavras-Chave #RETROTRAPEZOID NUCLEUS #INHALED ANESTHETICS #POTASSIUM CHANNELS #GENERAL-ANESTHESIA #IN-VITRO #RATS #CHEMOSENSITIVITY #SENSITIVITY #MECHANISMS #EXPRESSION #Neurosciences
Tipo

article

original article

publishedVersion