Intravenous anesthesia

Abstract

Anesthesia and Pain Medicine. 2003 Dec. 7(4): 160-165
ⓒ Korean Society for Intravenous Anesthesia
  
 
 
Effects of Propofol on the Activity of Glutamate Transporter Type 3 Expressed in Xenopus Oocytes: The Role of Protein Kinase C
Sang-Hwan Do, M.D., Ph.D.*, Jin-Hee Kim, M.D.*, Byung-Moon Ham, M.D., Ph.D.* and Zhiyi Zuo, M.D., Ph.D.
*Department of Anesthesiology, Seoul National University College of Medicine, Seoul, Korea, Department of Anesthesiology, Seoul City Boramae Hospital, Seoul, Korea, Department of Anesthesiology, University of Virginia Health System, Charlottesville, VA, USA
 

BACKGROUND: Glutamate transporters play a key role of removing extracellular glutamate which is the major excitatory neurotransmitter. Increased activities of glutamate transporter, EAAT3 were observed in volatile anesthetics and local anesthetics. We investigated the effects of propofol on the glutamate transporter EAAT3 and the role of protein kinase C (PKC) in mediating these effects.
METHODS: EAAT3 was expressed in Xenopus oocytes by injection of EAAT3 mRNA. After 3 day-incubation, Xenopus oocytes were exposed to 3, 10, 30, 100, and 300 muM of propofol for 3 min. Using two-electrode voltage clamp, membrane currents were recorded after the application of L-glutamate (30 muM). Responses were quantified by integration of the current trace and compared with control.
RESULTS: Propofol increased glutamate-induced inward currents significantly at two tested concentrations (30 and 100 muM) but not at other concentrations. Propofol (30 muM) significantly increased Vmax, but not Km of EAAT3 for glutamate. The combination of phorbol-12-myrisate-13-acetate (PMA, a PKC activator) and propofol did not increase the responses further compared with PMA or propofol alone. Three PKC inhibitors (staurosporine, calphostin C, and chelerythrine) did not affect basal EAAT3 activity but significantly inhibited the propofol-enhanced EAAT3 activity.
CONCLUSIONS: Our results demonstrated that propofol enhances EAAT3 activity at clinically relevant concentrations and PKC may mediate these effects. They suggest that the effects of propofol on EAAT activity may be a mechanism for propofol-induced anesthesia, anti-convulsion and neuroprotection.
 
Key words : EAAT3, propofol, protein kinase C, voltage clamp, Xenopus oocyte
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