Complex modulation of the cold receptor TRPM8 by volatile anaesthetics and its role in complications of general anaesthesia.

Abstract:

:The mechanisms by which volatile general anaesthetics (VAs) produce a depression of central nervous system are beginning to be better understood, but little is known about a number of side effects. Here, we show that the cold receptor transient receptor potential melastatin 8 (TRPM8) undergoes a complex modulation by clinical concentrations of VAs in dorsal root ganglion neurons and HEK-293 cells heterologously expressing TRPM8. VAs produced a transient enhancement of TRPM8 through a depolarizing shift of its activation towards physiological membrane potentials, followed by a sustained TRPM8 inhibition. The stimulatory action of VAs engaged molecular determinants distinct from those used by the TRPM8 agonist. Transient TRPM8 activation by VAs could explain side effects such as inhibition of respiratory drive, shivering and the cooling sensation during the beginning of anaesthesia, whereas the second phase of VA action, that associated with sustained TRPM8 inhibition, might be responsible for hypothermia. Consistent with this, both hypothermia and the inhibition of respiratory drive induced by VAs are partially abolished in Trpm8-knockout animals. Thus, we propose TRPM8 as a new clinical target for diminishing common and serious complications of general anaesthesia.

journal_name

J Cell Sci

journal_title

Journal of cell science

authors

Vanden Abeele F,Kondratskyi A,Dubois C,Shapovalov G,Gkika D,Busserolles J,Shuba Y,Skryma R,Prevarskaya N

doi

10.1242/jcs.131631

subject

Has Abstract

pub_date

2013-10-01 00:00:00

pages

4479-89

issue

Pt 19

eissn

0021-9533

issn

1477-9137

pii

jcs.131631

journal_volume

126

pub_type

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