Antiepileptic drugs--calcium current interaction in cultured human neuroblastoma cells.
The voltage-dependent calcium channel current (ICa) in the neuroblastoma cell line of human origin (NB-I) was studied by the whole-cell clamp recording. Three types of ICa were identified in NB-I cells. Our electrophysiological and pharmacological findings have suggested that these three types of ICa are consistent with the T-, N- and L-type ICa, respectively. Phenytoin (PHT) inhibited T-type ICa by 13.0% at a concentration of 5 microM, and L-type ICa by 6.3% at a concentration of 100 microM. At a concentration of 100 microM, carbamazepine (CBZ) inhibited T- and L-type ICa by 6.0% and 5.9%, respectively. At a concentration of 50 microM, sodium valproate (VPA) blocked T- and L-type ICa by 6.1% and 47.5%, respectively. At a concentration of 50 microM, zomisamide (ZNS) inhibited T- and L-type ICa by 38.3% and 41.9%, respectively. Na+ channel blockade has been reported to be responsible for the clinical efficacy of PHT or CBZ. Inhibition of T-type ICa by PHT may enhance the efficacy of its anticonvulsant action. CBZ had little effect on ICa. The anticonvulsant activity may be related to the blockade of T-type ICa in the case of VPA and ZNS.
Kito
M
M
Department of Pediatrics, Nagoya University School of Medicine, Japan.
Maehara
M
M
Watanabe
K
K
D000927:Anticonvulsants / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism; D002118:Calcium / Q000037:antagonists & inhibitors*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects*; D002478:Cells, Cultured / Q000187:drug effects; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism*
D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002118:Calcium