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Topiramate Blocks Kainate‐Evoked Cobalt Influx into Cultured Neurons
Author(s) -
Skradski Shana,
White H. Steve
Publication year - 2000
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1157.2000.tb02171.x
Subject(s) - dnqx , kainate receptor , ampa receptor , nmda receptor , glutamate receptor , pharmacology , kainic acid , chemistry , receptor , biology , biochemistry
Summary: Purpose : This study evaluated topiramate (TPM) antagonism of glutamate receptors activated by kainate. Methods : The ability of TPM (3–30 μ M ) to attenuate kainate (300 μ M )‐activated cobalt (Co 2+ ) flux through nonselective cation channels permeable to Co 2+ , Mn 2+ , and Ca 2+ into cultured cerebellar granule neurons [9–14 days in vitro (div)] was investigated. Results were compared with those obtained with the non‐ N ‐methyl‐ d ‐aspartate (non‐NMDA) antagonist 6,7‐dinitroquinoxalone‐2,3‐dione (DNQX) (10 μ M ). Results : Topiramate produced a concentration‐ and time‐dependent inhibition of Co 2+ uptake into cerebellar granule cells cultured 9–11 div. Inhibition was evident at 10 μ M , and complete inhibition was observed at 30 μ M . Maximal inhibition of Co 2+ uptake required pretreatment with TPM for ges;30 minutes before stimulation by kainate. The effect of 30 μ M TPM on Co 2+ uptake was similar to that of 10 μ M DNQX. However, TPM, unlike DNQX, did not affect kainate‐evoked Co 2+ uptake into older neurons (i.e., 13–14 div). Conclusions : These results provide additional support for an antagonistic effect of TPM on some types of α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐proprionic acid (AMPA) and/or kainate receptors, and specifically suggest that TPM interacts with a Ca 2+ ‐permeable non‐NMDA receptor that is develop‐mentally regulated. This observation may provide insight into the molecular biology underlying the pathophysiology of seizure disorders and antiepileptic drug resistance.