Bidirectional regulation of intravenous anes⁃thetic etomidate on TREK-1 potassium channel

摘要

OBJECTIVE Two-pore domain potassium channel subtype TREK-1 was widely proved to be activated by inhalational anesthet⁃ics such as chloroform,diethyl ether,halothane,and isoflurane.But little is known about whether TREK-1 was also a potentially important target of intravenous anesthetics.Etomidate is a popularly used intravenous anesthetic with good safety in clinic.The action of etomidate on TREK-1 was seldom reported.METHODS AND RESULTS By using patch-clamp whole-cell recording tech⁃niques,we found for the first time that etomidate could bidirectionally regulate the TREK-1 potassi⁃um channel in CHO/TREK-1 cells.TREK-1 current amplitudes were observed after the administra⁃tion of etomidate at concentrations ranging from 3 to 100μmol·L-1.Etomidate activated TREK-1 current at concentrations of 3,10,and 15μmol·L-1 with maximum activation at 10μmol·L-1.Interest⁃ingly,at higher concentrations from 20 to 100μmol·L-1,etomidate inhibited TREK-1 current in a concentration-dependent way.According to the concentration-response curve,the fitted criti⁃cal concentration of etomidate between TREK-1 activation and inhibition was 20.7μmol·L-1,which close to the result that etomidate had no obvious effect on TREK-1 at 20μmol·L-1.In addition,etomidate 10μmol·L-1 induced a significant mem⁃brane potential hyperpolarization while etomidate 30μmol·L-1 showed obvious membrane potential depolarization.Furthermore,the bidirectional regulation still existed when the extracellular pH of CHO/TREK-1 cells was decreased.CONCLUSION TREK-1 is activated by etomi⁃date at clinically relevant concentrations but inhib⁃ited by supraclinical concentrations of etomidate,which is different to other volatile anesthetics.TREK-1 might be a potential target for anesthetic such as etomidate and the complicated bidirec⁃tional regulation mechanism of etomidate needed to be fully studied in the future.