Dissociation of synchronization and excitability in furosemide blockade of epileptiform activity.
Furosemide, a chloride cotransport inhibitor, reversibly blocked synchronized burst discharges in hippocampal slices without reducing the pyramidal cell response to single electrical stimuli. Images of the intrinsic optical signal acquired during these slice experiments indicated that furosemide coincidentally blocked changes in extracellular space. In urethane-anesthetized rats, systemically injected furosemide blocked kainic acid-induced electrical discharges recorded from cortex. These results suggest that (i) neuronal synchronization involved in epileptiform activity can be dissociated from synaptic excitability; (ii) nonsynaptic mechanisms, possibly associated with furosemide-sensitive cell volume regulation, may be critical for synchronization of neuronal activity; and (iii) agents that affect extracellular volume may have clinical utility as antiepileptic drugs.
Hochman
D W
DW
Department of Neurological Surgery, University of Washington, Seattle 98195, USA.
Baraban
S C
SC
Owens
J W
JW
Schwartzkroin
P A
PA
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001640:Bicuculline / Q000494:pharmacology; D004558:Electric Stimulation; D018728:Entorhinal Cortex / Q000502:physiology; D005110:Extracellular Space / Q000187:drug effects / Q000502:physiology; D005260:Female; D005665:Furosemide / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000187:drug effects
D000927:Anticonvulsants; D005665:Furosemide; D015761:4-Aminopyridine; D008274:Magnesium; D011188:Potassium; D007608:Kainic Acid; D001640:Bicuculline