Effects of S(+)-efonidipine on the rabbit sinus node action potential and calcium channel subunits Ca(V)1.2, Ca(V)1.3 and Ca(V)3.1.
The effect of S(+)-efonidipine on sinus node action potential and calcium channel α-subunits was examined. The slope of the phase 4 depolarization of isolated rabbit sinus node tissue was significantly reduced by S(+)-efonidipine (1 μM), slightly reduced by nifedipine (1 μM), but was not affected by R(-)-efonidipine. S(+)-efonidipine (1 μM), inhibited the expressed Ca(V)1.2, Ca(V)1.3 and Ca(V)3.1 channel currents by 75.7%, 75.3% and 94.0%, nifedipine 84.0%, 43.2% and 14.9%, and R(-)-efonidipine 30.0%, 19.6% and 92.8%, respectively. Thus, the prolongation of the phase 4 depolarization of the rabbit sinus node by S(+)-efonidipine may be explained by blockade of the Ca(V)1.3 channel current.
Tanaka
Hikaru
H
Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences, Funabashi, Chiba 274-8510, Japan. htanaka@phar.toho-u.ac.jp
Namekata
Iyuki
I
Ogawa
Toru
T
Tsuneoka
Yayoi
Y
Komikado
Chisa
C
Takahara
Akira
A
Iida-Tanaka
Naoko
N
Izumi-Nakaseko
Hiroko
H
Tsuru
Hiromichi
H
Adachi-Akahane
Satomi
S
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006224:Cricetinae; D003864:Depression, Chemical; D004095:Dihydropyridines / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007536:Isomerism; D007700:Kinetics; D008297:Male; D009596:Nitrophenols / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D011994:Recombinant Proteins; D012849:Sinoatrial Node / Q000187:drug effects* / Q000502:physiology
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004095:Dihydropyridines; C419385:L-type calcium channel alpha(1C); D009596:Nitrophenols; D009943:Organophosphorus Compounds; D020033:Protein Isoforms; D021122:Protein Subunits; D011994:Recombinant Proteins; C066425:efonidipine