A selective T-type Ca2+ channel blocker R(-) efonidipine.
Recently, novel compound R(-) efonidipine was reported to selectively block low-voltage-activated (LVA or T-type) Ca2+ channels in peripheral organs. We examined how R(-) efonidipine acts on T-type and high-voltage-activated (HVA) Ca2+ channels in mammalian central nervous system (CNS) neurons. Furthermore, we compared the effects of R(-) efonidipine with those of flunarizine and mibefradil on both T-type and HVA Ca2+ channels in rat hippocampal CA1 neurons by using the nystatin perforated-patch clamp technique. Flunarizine and mibefradil nonselectively inhibited both T-type and HVA Ca2+ channels, though the dose-dependent blocking potency of flunarizine on T-type Ca2+ channels was slightly stronger than that of mibefradil. In contrast, R(-) efonidipine inhibited only T-type Ca2+ channels and did not show any effect on HVA Ca2+ channels. The inhibitory actions of R(-) efonidipine or flunarizine were similar on both Ba2+ and Ca2+ current components passing through T-type Ca2+ channels. In addition, flunarizine but not R(-) efonidipine inhibited voltage-dependent Na+ channels and Ca2+-activated K+ channels. Thus, it appears that R(-) efonidipine is a selective blocker for T-type Ca2+ channels. It could be used as a pharmacological tool in future studies on T-type Ca2+ channels.
Shin
Min-Chul
MC
Research Division for Life Sciences, Kumamoto Health Science University, Kumamoto, 861-5598, Japan.
Kim
Chang-Ju
CJ
Min
Byung-Il
BI
Ogawa
Sachie
S
Tanaka
Eiichiro
E
Akaike
Norio
N
D000818:Animals; D001464:Barium / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D020747:Calcium Channels, T-Type / Q000187:drug effects* / Q000378:metabolism; D004095:Dihydropyridines / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005444:Flunarizine / Q000008:administration & dosage / Q000494:pharmacology; D020748:Mibefradil / Q000008:administration & dosage / Q000494:pharmacology; D009596:Nitrophenols / Q000008:administration & dosage / Q000494:pharmacology*; D009761:Nystatin; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects / Q000378:metabolism; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020747:Calcium Channels, T-Type; D004095:Dihydropyridines; D009596:Nitrophenols; D009943:Organophosphorus Compounds; D024681:Potassium Channels, Calcium-Activated; D015222:Sodium Channels; D009761:Nystatin; D001464:Barium; D020748:Mibefradil; C066425:efonidipine; D005444:Flunarizine; D002118:Calcium