Actions of mibefradil, efonidipine and nifedipine block of recombinant T- and L-type Ca channels with distinct inhibitory mechanisms.
We compared detailed efficacy of efonidipine and nifedipine, dihydropyridine analogues, and mibefradil using recombinant T- and L-type Ca2+ channels expressed separately in mammalian cells. All these Ca2+ channel antagonists blocked T-type Ca2+ channel currents (I(Ca(T))) with distinct blocking manners: I(Ca(T)) was blocked mainly by a tonic manner by nifedipine, by a use-dependent manner by mibefradil, and by a combination of both manners by efonidipine. IC50s of these Ca2+ channel antagonists to I(Ca(T)) and L-type Ca2+ channel current (I(Ca(L))) were 1.2 micromol/l and 0.14 nmol/l for nifedipine; 0.87 and 1.4 micromol/l for mibefradil, and 0.35 micromol/l and 1.8 nmol/l for efonidipine, respectively. Efonidipine, a dihydropyridine analogue, showed high affinity to T-type Ca2+ channel.
Lee
Tae-Seong
TS
Department of Cardiovascular Science, Oita University School of Medicine, Oita, Japan.
Kaku
Toshihiko
T
Takebayashi
Satoshi
S
Uchino
Tomoko
T
Miyamoto
Shinji
S
Hadama
Tetsuo
T
Perez-Reyes
Edward
E
Ono
Katsushige
K
D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D002460:Cell Line; D004095:Dihydropyridines / Q000494:pharmacology*; D006801:Humans; D020748:Mibefradil / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology*; D009596:Nitrophenols / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004095:Dihydropyridines; D009596:Nitrophenols; D009943:Organophosphorus Compounds; D011994:Recombinant Proteins; D020748:Mibefradil; C066425:efonidipine; D009543:Nifedipine