Abstract:
: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.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Guyon A,Cathala L,Paupardin-Tritsch D,Eugène Ddoi
10.1016/s0028-3908(02)00178-8subject
Has Abstractpub_date
2002-09-01 00:00:00pages
750-63issue
4eissn
0028-3908issn
1873-7064pii
S0028390802001788journal_volume
43pub_type
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