DISSOCIATION OF SYNCHRONIZATION AND EXCITABILITY IN FUROSEMIDE BLOCKADE OF EPILEPTIFORM ACTIVITY

Furosemide, a chloride cotransport inhibitor, reversibly blocked synch ronized burst discharges in hippocampal slices without reducing the py ramidal cell response to single electrical stimuli. Images of the intr insic optical signal acquired during these slice experiments indicated that furosemide coincidentally blocked changes in extracellular space . In urethane-anesthetized rats, systemically injected furosemide bloc ked kainic acid-induced electrical discharges recorded from cortex. Th ese results suggest that (i) neuronal synchronization involved in epil eptiform activity can be dissociated from synaptic excitability; (ii) nonsynaptic mechanisms, possibly associated with furosemide-sensitive cell volume regulation, may be critical for synchronization of neurona l activity; and (iii) agents that affect extracellular volume may have clinical utility as antiepileptic drugs.