I L White1, N P Franks, R Dickinson. 1. Department of Anaesthetics and Intensive Care, Faculty of Medicine, Imperial College London, Chelsea and Westminster Campus, 369 Fulham Road, London SW10 9NH, UK.
Abstract
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.
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.
Authors: Pavle M Joksovic; Marco Weiergräber; WooYong Lee; Henrik Struck; Toni Schneider; Slobodan M Todorovic Journal: J Neurosci Date: 2009-02-04 Impact factor: 6.167
Authors: Mariia Koziakova; Katie Harris; Christopher J Edge; Nicholas P Franks; Ian L White; Robert Dickinson Journal: Br J Anaesth Date: 2019-08-27 Impact factor: 9.166