Effects of Ca2+ antagonists and antiepileptics on tetrodotoxin-sensitive Ca(2+)-conducting channels in isolated rat hippocampal CA1 neurons.
All Ca2+ antagonists blocked tetrodotoxin-sensitive Ca2+ current (TTX-ICa) more potently than Na+ current (INa). Phenytoin and MK-801, at concentrations which had no effect on INa, could block TTX-ICa concentration-dependently. Valproic acid and phenobarbital had no effect on both TTX-ICa and INa. In particular, flunarizine and phenytoin have more potent inhibitory effects on TTX-ICa than other test drugs. These results suggest that the abnormal excess-excitation of TTX-sensitive Ca(2+)-conducting channels may be one of the trigger factors generating epilepsy.
Takahashi
K
K
Research Laboratories, Roussel Morishita Co., Ltd., Shiga, Japan.
Kameda
H
H
Kataoka
M
M
Ueno
S
S
Akaike
N
N
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004110:Diltiazem / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005444:Flunarizine / Q000494:pharmacology; D006624:Hippocampus / Q000502:physiology*; D007700:Kinetics; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009529:Nicardipine / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology; D011712:Pyramidal Tracts / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology*; D014635:Valproic Acid / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D013779:Tetrodotoxin; D014635:Valproic Acid; D010672:Phenytoin; D016291:Dizocilpine Maleate; D012964:Sodium; D014700:Verapamil; D009529:Nicardipine; D004110:Diltiazem; D005444:Flunarizine; D002118:Calcium; D010634:Phenobarbital