[Epileptic seizures from etomidate? The human Kv1.1 potassium channel in humans].
OBJECTIVE
It is a matter of dispute whether etomidate exhibits an epileptogenic action. It is also disputed whether frequently observed myocloni induced by etomidate are related to seizure-like activity in the EEG. The clinical effects of anaesthetic agents reflect their molecular action. A possible epileptogenic action of etomidate should, therefore, result from action on a molecular target that has yet to be identified. Suppression of Kv1.1 channels may be associated with epilepsy in men. Inhibition of Kv1.1 channels by etomidate at clinically relevant concentrations would, thus, argue in favour of an epileptogenic action of etomidate.


METHODS
Patch-clamp recordings of the pharmacological action of etomidate on cloned and functionally expressed human Kv1.1 channels.


RESULTS
Etomidate inhibits human Kv1.1 channels in a concentration-dependent and reversible manner. The IC50-value is 400 microM, the Hill-coefficient is 2. The ratio of free clinical plasma concentrations and the IC50-value is 0.006. At plasma concentrations determined in a clinical setting Kv1.1 channels would be suppressed by less than 0.01%.


CONCLUSIONS
The small effect of etomidate on human Kv1.1 channels at these concentrations questions an epileptogenic action of etomidate caused by inhibition of Kv1.1 channels.
Friederich
P
P
Klinik und Poliklinik für Anästhesiologie, Universitätsklinik Eppendorf, Hamburg. patrick.friederich@zmmh.uni-hamburg.de
Trellakis
S
S
Urban
B W
BW
D002478:Cells, Cultured; D003001:Cloning, Molecular; D005045:Etomidate / Q000009:adverse effects*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects*; D051662:Kv1.1 Potassium Channel; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated
D006993:Hypnotics and Sedatives; C496946:KCNA1 protein, human; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051662:Kv1.1 Potassium Channel; D005045:Etomidate