Species difference in the contribution of T-type calcium current to cardiac pacemaking as revealed by r(-)-efonidipine.
The contribution of the T-type Ca2+ current to cardiac pacemaking was examined in isolated right atrial tissue from the mouse, guinea pig, and rabbit using a specific blocker, R(-)-efonidipine. At 10(-6) M, R(-)-efonidipine produced negative chronotropy, which was prominent in the mouse and small but significant in the guinea pig. No effect was observed in the rabbit. Microelectrode recordings revealed that R(-)-efonidipine significantly prolongs the pacemaker (phase 4) depolarization of the sinoatrial-node action potential in the mouse and guinea pig. These results provide the first pharmacological evidence that the contribution of T-type Ca2+ current to cardiac pacemaking differs among experimental animal species.
Tanaka
Hikaru
H
Department of Pharmacology, Toho University Faculty of Pharmaceutical Sciences, Japan.
Komikado
Chisa
C
Namekata
Iyuki
I
Nakamura
Hideki
H
Suzuki
Mariko
M
Tsuneoka
Yayoi
Y
Shigenobu
Koki
K
Takahara
Akira
A
D000200:Action Potentials; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020747:Calcium Channels, T-Type / Q000187:drug effects* / Q000378:metabolism; D004095:Dihydropyridines / Q000494:pharmacology*; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D051379:Mice; D008839:Microelectrodes; D009596:Nitrophenols / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D011817:Rabbits; D012849:Sinoatrial Node / Q000187:drug effects* / Q000378:metabolism; D013045:Species Specificity; D013997:Time Factors
D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D004095:Dihydropyridines; D009596:Nitrophenols; D009943:Organophosphorus Compounds; C066425:efonidipine