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Dual mechanisms of GABA a response inhibition by β‐lactam antibiotics in the pyramidal neurones of the rat cerebral cortex
Author(s) -
Fujimoto Mika,
Munakata Mitsutoshi,
Akaike Norio
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.tb15957.x
Subject(s) - neuroscience , cerebral cortex , lactam , chemistry , biology , stereochemistry
1 The effects of β‐lactam antibiotics on the γ‐aminobutyric acid (GABA)‐induced Cl − current were investigated in pyramidal neurones freshly dissociated from the rat frontal cortex by the use of a nystatin‐perforated patch recording mode under voltage‐clamp conditions. 2 The GABA‐induced inward current increased in a concentration‐dependent manner with an EC 50 of 6.7 × 10 −6 m at a holding potential of −40 mV. The GABA response was accompanied by an increase in the membrane conductance and reversed at near the Cl − equilibrium potential. 3 All β‐lactams (penicillin, imipenem, aztreonam and cefotiam) inhibited the 10 −5 m GABA‐induced response in a concentration‐dependent manner with an IC 50 and Hill coefficient of 1.3 × 10 −3 m and 0.64 for penicillin, 9.6 × 10 −4 m and 0.83 for imipenem, 2.5 × 10 −3 m and 9.99 for aztreonam, and 2.9 × 10 −4 m and 1.03 for cefotiam. 4 Imipenem inhibited the GABA‐response competitively while penicillin inhibited the same response in a noncompetitive fashion. 5 The inhibitory action of imipenem showed no voltage‐dependency, whereas the effect of penicillin was voltage‐dependent. 6 It is thus proposed that some classes of β‐lactams, including imipenem, may have a mechanism that is different from penicillin and competitively affects the GABA A receptor.