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Potentiation, activation and blockade of GABA A receptors of clonal murine hypothalamic GT1‐7 neurones by propofol
Author(s) -
Adodra Snehal,
Hales Tim G.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb15903.x
Subject(s) - propofol , bicuculline , gabaa receptor , long term potentiation , gaba receptor antagonist , reversal potential , electrophysiology , patch clamp , antagonist , chemistry , receptor , pharmacology , biophysics , anesthesia , endocrinology , medicine , biology
1 The actions of GABA and the intravenous general anaesthetic propofol (2,6‐düsopropylphenol) on GABA A receptors of self‐replicating GT1‐7 hypothalamic neurones were investigated by the patch clamp technique. 2 GABA (1 μm‐1 mM) dose‐dependently activated inward currents with an EC 50 of 27 μm, recorded from whole cells voltage‐clamped at —60 mV. GABA (100 μ m )‐activated currents reversed at the Cl − equilibrium potential. 3 Propofol (0.1 −100 μ m ) dose‐dependently potentiated GABA (100 μ m )‐evoked currents with an EC 50 of 5 μ m . 4 In the absence of GABA, propofol (10 μ m ‐1 mM) activated small inward currents with a reversal potential similar to the CI − equilibrium potential. The peak current amplitudes activated by propofol were only 31% of those activated by GABA in the same cells. 5 Like GABA (100 μ m )‐activated currents, propofol (100 μ m )‐activated currents were inhibited by the GABA A receptor antagonist, bicuculline (10 μ m ) and were abolished by Zn 2+ (100 μ m ). 6 Propofol (10, 30 and 100 μ m ) dose‐dependently activated currents in the absence of GABA. However, the peak amplitude of currents activated by propofol declined with concentrations > 100 μ m . The cessation of application of a high dose of propofol (1 mM) was associated with a current ‘surge’. 7 The surge current, seen after application of propofol (1 mM), had a reversal potential similar to the CI − equilibrium potential. The ratio between peak current amplitude in the presence of propofol (1 mM) and surge current amplitude after propofol application, were not dependent on holding potential. Thus, it is unlikely that the surge current represents reversal of a voltage‐dependent block of GABA A receptors by propofol. 8 The amplitude of the surge current exceeded the amplitude of the initial propofol (1 mM)‐evoked current following brief applications, but declined after prolonged applications of the drug. 9 The observed modulatory actions of propofol may be due to separate potentiation, activation and inhibitory sites for this anaesthetic agent on GT1‐7 cell GABA A receptors.