Referenced in: none

Automatically associated channels: Kv12.1

Title: Inhibition of glutamatergic activation of extracellular signal-regulated protein kinases in hippocampal neurons by the intravenous anesthetic propofol.

Authors: Jonathan Kozinn, Limin Mao, Anish Arora, Lu Yang, Eugene E Fibuch, John Q Wang

Journal, date & volume: Anesthesiology, 2006 Dec , 105, 1182-91

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/17122581

Abstract
Intravenous anesthetics cause amnesia, but the underlying molecular mechanisms are poorly understood. Recent studies reveal a significant role of extracellular signal-regulated protein kinases (ERKs) in controlling synaptic plasticity and memory formation. As a major synapse-to-nucleus superhighway, ERK transmits N-methyl-D-aspartate (NMDA) receptor signals to inducible transcriptional events essential for NMDA receptor-dependent forms of synaptic plasticity and memory. This study investigated the role of the widely used intravenous anesthetic propofol in regulating NMDA receptor-dependent ERK phosphorylation.The possible effect of propofol on NMDA receptor-mediated ERK phosphorylation was detected in cultured rat hippocampal neurons with Western blot analysis.The authors found that propofol at clinical relevant concentrations (1-10 microm) reduced NMDA receptor-mediated ERK phosphorylation. This reduction was independent of gamma-aminobutyric acid transmission. The inhibition of the NMDA receptor seems to contribute to the effect of propofol on NMDA-stimulated ERK phosphorylation, because propofol reduced constitutive NMDA receptor NR1 subunit phosphorylation and impaired NMDA receptor-mediated Ca influx. Furthermore, by inhibiting the ERK pathway, propofol blocked NMDA receptor-dependent activation of two key transcription factors, Elk-1 and cyclic adenosine monophosphate response element-binding protein (CREB), and, as a result, attenuated Elk-1/CREB-dependent reporter gene (c-Fos) expression.These results suggest that propofol possesses the ability to inhibit NMDA receptor activation of the ERK pathway and subsequent transcriptional activities in hippocampal neurons. These findings indicate a new avenue to explore a transcription-dependent mechanism that may underlie anesthetic interference with synaptic plasticity related to amnesic properties of intravenous anesthetics.