Role of chloride-homeostasis in the inhibitory control of neuronal network oscillators.
1. Spontaneous synaptic activity in networks formed by dissociated neurons from embryonic rat midbrain was analyzed in tight seal whole cell recordings. 2. Application of furosemide (0.5 mM) to the cell and its surrounding area increased the frequency of spontaneous synaptic currents. Incubation of the culture with furosemide resulted in "rhythmic" burst activity. 3. Furosemide (0.1-0.5 mM) changed equilibrium potentials of inhibitory postsynaptic currents, gamma-aminobutyric acid-A (GABAA) or glycine receptor-mediated Cl- currents by a blockade of Cl(-)-outward transport. Furosemide did not alter the slope conductance of GABAA receptor-mediated currents. Membrane conductance and cell excitability were also unaffected. 4. We conclude that furosemide locked the activity of the network in "burst activity" mode through impairment of inhibition resulting from the disturbance of Cl- homeostasis.
Jarolimek
W
W
Institute of Physiology, University of Heidelberg, Germany.
Brunner
H
H
Lewen
A
A
Misgeld
U
U
D000818:Animals; D002478:Cells, Cultured; D002712:Chlorides / Q000502:physiology*; D004232:Diuretics / Q000494:pharmacology; D005665:Furosemide / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology*; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009118:Muscimol / Q000494:pharmacology; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism
D002712:Chlorides; D004232:Diuretics; D018755:GABA Agonists; D018091:Receptors, AMPA; D011963:Receptors, GABA-A; D009118:Muscimol; D005665:Furosemide