Furosemide modulation of GABA(A) receptors in dopaminergic neurones of the rat substantia nigra.
Furosemide is a diuretic which has been shown to decrease recombinant GABA(A) receptor (GABA(A)R)-mediated currents and also to block epileptiform discharges. Here, we show that furosemide actions on GABA(A)Rs of rat substantia nigra dopaminergic neurones depend on both furosemide and GABA(A)R agonist concentrations. The whole-cell currents induced by low concentrations of GABA (5 microM) or by the selective GABA(A)R agonist isoguvacine (7-25 microM) were enhanced by 200 microM furosemide. However, furosemide did not affect GABA(A)R currents induced by 60 microM isoguvacine and even decreased those induced by 200 microM isoguvacine. At the single-channel level, furosemide had comparable effects. It increased the open time proportion with 7 microM isoguvacine but had no significant effect on the open time proportion with 60 microM isoguvacine. These effects resulted from a differential action on the multiple conductance levels activated by GABA(A)R agonists. The concentration-response relationship to isoguvacine in the whole-cell mode revealed the presence of a high and a low apparent affinity GABA(A)R population (EC(50) 4.8 vs 89 microM). These two populations of receptors coexist in the same dopaminergic neurone. They are both furosemide-sensitive and may represent different GABA(A)R subunit assemblies.
D000818:Animals; D002469:Cell Separation; D003627:Data Interpretation, Statistical; D004298:Dopamine / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005665:Furosemide / Q000494:pharmacology*; D018755:GABA Agonists / Q000494:pharmacology; D018757:GABA Modulators; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D007539:Isonicotinic Acids / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects*; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects*
D018755:GABA Agonists; D018757:GABA Modulators; D007473:Ion Channels; D007539:Isonicotinic Acids; D011963:Receptors, GABA-A; D005665:Furosemide; D004298:Dopamine; C015300:isoguvacine