Premium
The difference between sleep and anaesthesia is in the intracellular signal: propofol and GABA use different subtypes of the GABA A receptor β subunit and vary in their interaction with actin
Author(s) -
Björnström K.,
Eintrei C.
Publication year - 2003
Publication title -
acta anaesthesiologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 107
eISSN - 1399-6576
pISSN - 0001-5172
DOI - 10.1034/j.1399-6576.2003.00007.x
Subject(s) - tyrosine phosphorylation , tyrosine , cytoskeleton , gabaa receptor , actin cytoskeleton , phosphorylation , microbiology and biotechnology , gaba receptor , receptor , biology , medicine , endocrinology , pharmacology , biochemistry , cell
Background: Propofol is known to interact with the γ‐aminobutyric acid A (GABA A ) receptor, however, activating the receptor alone is not sufficient for producing anaesthesia. Methods: To compare propofol and GABA, their interaction with the GABA A receptor β 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 β 2 (MW 54 and 56 kDa) and β 3 (MW 57 kDa) subtypes. The increase was shown in both the cytoskeleton (β 2(54) and β 2(56) subtypes) and the cell membrane (β 2(54) and β 3 subtypes). Concurrently the 56 kDa β 2 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 β 2(56) and β 3 subtypes in the membrane and both β 2 subtypes in the cytoskeleton but no cytosolic tyrosine phosphorylation. Conclusion: The difference between propofol and GABA at the GABA A receptor was shown to take place in the membrane, where the β 2(54) was increased by propofol and instead the β 2(56) subtype was increased by GABA. Only propofol also tyrosine phosphorylated actin in the cell membrane and cytoskeletal fraction. This interaction between the GABA A receptor and actin might explain the difference between anaesthesia and physiological neuronal inhibition.