Effects of isoflurane and xenon on Ba2+-currents mediated by N-type calcium channels.
BACKGROUND
Isoflurane and xenon are inhalation general anaesthetics with differing clinical profiles and contrasting synaptic actions. Both agents have been shown to depress excitatory synaptic responses. Whether this is via pre-synaptic or post-synaptic mechanisms has not been determined clearly. N-type calcium channels are a putative pre-synaptic target for these agents. We tested whether N-type calcium channels were sensitive to isoflurane and xenon and whether there was any stereoselectivity in the effect of isoflurane.


METHODS
We used patch-clamp electrophysiology on isolated HEK293 cells stably expressing N-type calcium channels to investigate the effects of isoflurane and xenon on barium currents mediated by N-type calcium channels.


RESULTS
Racemic isoflurane caused a concentration-dependent reduction (11-35%) in the peak current through the N-type channels in the concentration range 0.15-1.22 mM. In the clinically relevant concentration range the inhibition was small. At an isoflurane concentration of 0.31 mM (equivalent to 1 MAC), the peak N-type current was inhibited by 14 (1)%. The optical isomers of isoflurane were found to be equally potent at inhibiting currents through N-type channels. The inert gas anaesthetic xenon was found to have no measureable effect on N-type channels at a concentration of 3.4 mM (approximately 1 MAC).


CONCLUSIONS
These results suggest that N-type calcium channels are not the targets mediating general anaesthesia with these two inhalation agents.
White
I L
IL
Department of Anaesthetics and Intensive Care, Faculty of Medicine, Imperial College London, Chelsea and Westminster Campus, 369 Fulham Road, London SW10 9NH, UK.
Franks
N P
NP
Dickinson
R
R
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001464:Barium / Q000378:metabolism*; D020864:Calcium Channels, N-Type / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D015640:Ion Channel Gating / Q000187:drug effects; D007530:Isoflurane / Q000737:chemistry / Q000494:pharmacology*; D007536:Isomerism; D018408:Patch-Clamp Techniques; D051381:Rats; D013329:Structure-Activity Relationship; D014978:Xenon / Q000494:pharmacology*
D018685:Anesthetics, Inhalation; D020864:Calcium Channels, N-Type; D001464:Barium; D014978:Xenon; D007530:Isoflurane