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The influence of the γ 2L subunit on the modulation of responses to GABA A receptor activation
Author(s) -
Home A.L.,
Harkness P.C.,
Hadingham K.L.,
Whiting P.,
Kemp J.A.
Publication year - 1993
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.1476-5381.1993.tb12866.x
Subject(s) - flunitrazepam , beta (programming language) , alpha (finance) , gabaa receptor , chemistry , gamma aminobutyric acid , biophysics , receptor , biochemistry , biology , medicine , construct validity , nursing , computer science , patient satisfaction , programming language
1 Whole‐cell patch clamp recordings were made from L‐cells transfected with 2 combinations of subunits of the GABA A receptor. Log concentration‐response curves were constructed to γ‐aminobutyric acid (GABA) on α 1 ,β 1 ,γ 2L containing cells and compared to those from α 1 ,β 1 containing cells. The effects of flunitrazepam, pentobarbitone and alphaxalone on the concentration‐response relationships were also examined. 2 From the log concentration‐response curves, GABA had a mean (± s.e.mean) pEC 50 = 5.2 ± 0.09 and slope factor = 1.7 ± 0.02 on α 1 β 1 ,γ 2L cells which were significantly different from the values obtained from α 1 ,β 1 cells where the pEC 50 = 5.6 ± 0.02 and the slope = 1.5 ±0.02. 3 Flunitrazepam produced a parallel leftward shift of GABA concentration‐response curves on α 1 ,β 1 ,γ 2L cells. The EC 50 for flunitrazepam = 6.3 ± 2.7 n m . No increase in the maxima of the GABA concentration‐response curves was found in the presence of flunitrazepam. Flunitrazepam did not potentiate responses from α 1 ,β 1 cells. 4 The log concentration‐response curves from both populations of cells were shifted to the left by equal amounts by pentobarbitone. A significant increase in the maximal response to GABA was also produced by pentobarbitone. This occurred at lower concentrations of pentobarbitone on α 1 ,β 1 cells. 5 Alphaxalone produced leftward shifts of GABA log concentration‐response curves of similar magnitudes in both populations of cells. Significant increases in the maxima were found at 100 n m in α 1 ,β 1 cells but not up to 1 μ m in α 1 ,β 1 ,γ 2L cells. 6 These results provide further evidence of the modulatory role of the γ 2L subunit of the GABA A receptor containing α 1 and β 1 subunits. As well as influencing the apparent affinity of GABA and conferring benzodiazepine modulation, it also appeared to regulate the increase in maximal response produced in the presence of barbiturates and steroids. This latter effect may imply that barbiturates and steroids increase the channel open‐state probability in the presence of GABA and that this effect is diminished by the presence of the γ 2L subunit.