The freezing lesion. III. The effects of diphenylhydantoin on potassium transport within nerve terminals from the primary foci.
Possible mechanisms by which dephenylhydantoin (DPH) controls seizures were examined. The effects of intraperitoneal DPH on seizure discharges within epileptogenic freeze lesions were correlated with DPH action on in vitro potassium uptake within synaptosomes isolated from the same freeze foci. When in vivo DPH suppressed seizure discharges, it stimulated in vitro potassium uptake within synaptosomes incubated in a high-Kplus (10 mM) media. With 2-5 mM Naplus and 10mM Kplus, DPH stimulation of synaptosome potassium uptake was reversed by ouabain. With 50 mM Naplus and 10 mM Kplus, DPH stimulation of potassium uptake was not reversed by ouabain. In low-Kplus (0.2-5 mM) media, DPH did not affect potassium uptake even when sodium concentrations were varied at 10-100 mM. In sham-operated controls and in non-epileptogenic lesions, the effects of DPH on synaptosome potassium uptake were identical to those previously reported in normal brains. These results strongly suggest that DPH controls the epileptogenic state by stimulating potassium uptake within synaptic terminals. DPH controls the epileptogenic state by stimulating potassium uptake within synaptic terminals. DPH enhances synaptic potassium uptake by stimulating the (Naplus-Kplus) pump and a second potassium uptake process which is insensitive to ouabain.
D000818:Animals; D002415:Cats; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism*; D004569:Electroencephalography; D004594:Electrophysiology / Q000187:drug effects*; D004827:Epilepsy / Q000209:etiology / Q000503:physiopathology*; D005615:Freezing; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D010042:Ouabain / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism*
D010042:Ouabain; D010672:Phenytoin; D011188:Potassium