Abstract
Furosemide is a diuretic which has been shown to decrease recombinant GABA A receptor (GABA AR)-mediated currents and also to block epileptiform discharges. Here, we show that furosemide actions on GABA ARs of rat substantia nigra dopaminergic neurones depend on both furosemide and GABA AR agonist concentrations. The whole-cell currents induced by low concentrations of GABA (5 μM) or by the selective GABA AR agonist isoguvacine (7–25 μM) were enhanced by 200 μM furosemide. However, furosemide did not affect GABA AR currents induced by 60 μM isoguvacine and even decreased those induced by 200 μM isoguvacine. At the single-channel level, furosemide had comparable effects. It increased the open time proportion with 7 μM isoguvacine but had no significant effect on the open time proportion with 60 μM isoguvacine. These effects resulted from a differential action on the multiple conductance levels activated by GABA AR agonists. The concentration-response relationship to isoguvacine in the whole-cell mode revealed the presence of a high and a low apparent affinity GABA AR population (EC 50 4.8 vs 89 μM). These two populations of receptors coexist in the same dopaminergic neurone. They are both furosemide-sensitive and may represent different GABA AR subunit assemblies.
Published Version
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