The difference between sleep and anaesthesia is in the intracellular signal: propofol and GABA use different subtypes of the GABA(A) receptor beta subunit and vary in their interaction with actin.
BACKGROUND
Propofol is known to interact with the gamma-aminobutyric acidA (GABA(A)) receptor, however, activating the receptor alone is not sufficient for producing anaesthesia.


METHODS
To compare propofol and GABA, their interaction with the GABAA receptor beta subunit and actin were studied in three cellular fractions of cultured rat neurons using Western blot technique.


RESULTS
Propofol tyrosine phosphorylated the GABA(A) receptor beta2 (MW 54 and 56 kDa) and beta3 (MW 57 kDa) subtypes. The increase was shown in both the cytoskeleton (beta2(54) and beta2(56) subtypes) and the cell membrane (beta2(54) and beta3 subtypes). Concurrently the 56 kDa beta2 subtype was reduced in the cytosol. Propofol, but not GABA, also tyrosine phosphorylated actin in the cell membrane and cytoskeletal fraction. Without extracellular calcium available, the amount of actin decreased in the cytoskeleton, but tyrosine phosphorylation was unchanged. GABA caused increased tyrosine phosphorylation of beta2(56) and beta3 subtypes in the membrane and both beta2 subtypes in the cytoskeleton but no cytosolic tyrosine phosphorylation.


CONCLUSIONS
The difference between propofol and GABA at the GABA(A) receptor was shown to take place in the membrane, where the beta2(54) was increased by propofol and instead the beta2(56) subtype was increased by GABA. Only propofol also tyrosine phosphorylated actin in the cell membrane and cytoskeletal fraction. This interaction between the GABAA receptor and actin might explain the difference between anaesthesia and physiological neuronal inhibition.
Björnström
K
K
Department of Anaesthesiology, Linköping University, Linköping, Sweden. karin.bjornstrom-karlsson@lio.se
Eintrei
C
C
D000199:Actins / Q000187:drug effects*; D000758:Anesthesia; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002462:Cell Membrane / Q000187:drug effects; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects; D003600:Cytosol / Q000187:drug effects; D007202:Indicators and Reagents; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure; D010766:Phosphorylation; D011233:Precipitin Tests; D015742:Propofol / Q000494:pharmacology*; D021122:Protein Subunits; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology*; D012890:Sleep / Q000502:physiology*; D013347:Subcellular Fractions / Q000187:drug effects / Q000648:ultrastructure; D014443:Tyrosine / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000199:Actins; D018686:Anesthetics, Intravenous; D007202:Indicators and Reagents; D021122:Protein Subunits; D011963:Receptors, GABA-A; D014443:Tyrosine; D005680:gamma-Aminobutyric Acid; D015742:Propofol