Intravenous anesthesia


Anesthesia and Pain Medicine. 2004 Dec. 8(4): 203-207
ⓒ Korean Society for Intravenous Anesthesia
Effects of Etomidate on the Activity of Glutamate Transporter EAAC1 Expressed in Xenopus Oocytes: The Role of Protein Kinase C
Chong-Soo Kim, M.D.*, Jung-Yeon Yun, M.D.*, and Sang-Hwan Do, M.D.*
*Department of Anesthesiology, Seoul National University College of Medicine, Seoul, Korea, Department of Anesthesiology, Seoul City Boramae Hospital, Seoul, Korea

Background: Glutamate transporters play a key role of removing extracellular glutamate which is the major excitatory neurotransmitter. Increased activities of glutamate transporter, EAAC1 were observed in volatile anesthetics, lidocaine and propofol. We investigated the effects of etomidate on the glutamate transporter EAAC1 and the role of protein kinase C (PKC) in mediating these effects.
Methods: EAAC1 was expressed in Xenopus oocytes by injection of EAAC1 mRNA. After 3 day- incubation, Xenopus oocytes were exposed to 0.03 10mum of etomidate for 3 min. Using two-electrode voltage clamp, membrane currents were recorded after the application of L-glutamate (30mum). Responses were quantified by integration of the current trace.
Results: Etomidate decreased glutamate-induced inward current in a concentration-dependent manner. Etomidate at 1mum significantly decreased Vmax, but not Km of EAAC1 for glutamate. The combination of staurosporine, an inhibitor for PKC, and etomidate did not decrease the response further compared with staurosporine or etomdiate alone. Phorbol-12-myrisate-13-acetate, a PKC activator, abolished the etomidate-reduced EAAC1 activity.
Conclusions: Our results demonstrated that etomidate, possibly via PKC, decreased EAAC1 activity at clinically relevant concentrations.
Key words : EAAC1, etomidate, protein kinase C, voltage clamp, Xenopus oocyte
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