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Vol. 55, Issue 1, 168-178, January 1999
-Aminobutyric Acid (GABA)-Activated
GABAA Receptor Channels Formed by 
Subunit-Containing
Isoforms
Neuroscience Program (T.R.N., M.B., R.L.M.) and Departments of
Neurology (J.F., R.L.M.) and
Physiology (R.L.M.), University of
Michigan, Ann Arbor, Michigan
A new 
-aminobutyric acid (GABA)A receptor (GABAR)
subunit class, 
, has recently been cloned and shown to form
functional channels when coexpressed with both 
and 
subunits. We
report that the combination of 13 subunit subtypes expressed
in L929 cells produced functional chloride ion channels that were both spontaneously active and gated by the application of extracellular GABA. When cells were voltage-clamped at -75 mV in the whole-cell configuration, holding currents of 50 to 300 pA associated with increased noise were consistently recorded. The application of pentobarbital and loreclezole, which increase GABAR currents, increased
the holding current, whereas the application of zinc and picrotoxin,
which reduce GABAR currents, reduced the holding current in a
concentration-dependent manner. Coexpression of 132L, 13
, 1, 3, 13, or subtypes did not
produce holding currents that were sensitive to picrotoxin (30 µM).
Cells expressing 1 3 subtypes had concentration-dependent
GABAR currents that were potentiated by pentobarbital, loreclezole, and
lanthanum and inhibited by zinc and furosemide. Spontaneous and GABAR
single-channel currents from 13 receptors had single-channel
conductances of ~24 pS. The biophysical properties and the effects of
allosteric modulators were similar for spontaneous and evoked GABAR
currents, suggesting that a single GABAR isoform was responsible for
both currents. These data extend the pharmacological characterization
of -containing GABARs and demonstrate that incorporation of the subunit permits spontaneous channel gating while
preserving the structural information necessary for GABA sensitivity.
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