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General anesthetics attenuate gap junction coupling in P19 cell line
Kirsten Wentlandt1, Peter L Carlen, Moshe Kushnir
1University Health Network, Toronto Western Research Institute, Division of Cellular and Molecular Biology, Toronto, Ontario, Canada.
Journal of Neuroscience Research
|June 23, 2005
Summary
General anesthetics like propofol and thiopental reduce gap junction communication in developing neural cells. However, clinically relevant concentrations of halothane did not affect this crucial intercellular signaling.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Gap junction communication is vital for neuronal and glial function in the mammalian nervous system.
- General anesthetics are known to affect neural signaling, but their impact on gap junctions requires further investigation.
Purpose of the Study:
- To investigate the effect of general anesthetics on gap junction-mediated communication in a P19 cell line.
- To determine if clinically relevant concentrations of propofol, thiopental, and halothane alter intercellular coupling.
Main Methods:
- Utilized a P19 cell line capable of differentiating into neuronal and glial cells.
- Employed dye coupling techniques using chlormethylbenzamido-1,1 dioctadecyl-3,3,3',3'-tetramethylindocarbocyamine (CM-DiI) and calcein-AM to assess gap junction permeability.
- Quantified intercellular connections via cell counting and flow cytometry up to 2 hours post-treatment.
Main Results:
- Clinically relevant concentrations of propofol (15 microM) and thiopental (10 microM) significantly attenuated gap junction permeability.
- Halothane at its clinically relevant concentration (0.64 mM) showed no effect on gap junction coupling.
- Very high concentrations of halothane (2.8 mM) inhibited dye transfer by approximately 90%.
Conclusions:
- Propofol and thiopental, at concentrations used clinically, depress gap junction coupling in a P19 cell line.
- Halothane, at concentrations pertinent to clinical anesthesia, does not attenuate gap junction communication in this cell model, despite its known effects at higher concentrations.