Electrophysiological effects of CD-349, a dihydropyridine-type calcium antagonist, on goat cardiac Purkinje fibers.
We examined the calcium antagonistic action of CD-349, a dihydropyridine derivative, on goat cardiac Purkinje fibers using the two-microelectrode voltage-clamp method. CD-349 at a concentration of 10(-5) M shortened the action potential duration without changing the maximum rise in the action potential (Vmax) in goat Purkinje fibers. CD-349 at 3 x 10(-7) to 3 x 10(-6) M inhibited the slow inward current (Isi) in a concentration-dependent manner. At the holding potential of -55 mV, CD-349 exerted a tonic block of Isi, and, furthermore, it exerted a use-dependent block at a frequency range of 1 Hz, but it did not exert a use-dependent block at 0.5 and 0.2 Hz. This may be because CD-349 delayed the recovery process from the inactivation of Isi. The amplitude of the block of Isi was larger at the holding potential of -45 mV than at -55 mV. The inactivation curve of Isi shifted toward a negative potential in the presence of CD-349. Nifedipine also exerted a tonic block of Isi. The onset of the action of nifedipine was quicker than that of CD-349 or nitrendipine. A use-dependent block at 1 Hz and delay of the recovery process from inactivation was also observed with nifedipine. The inactivation curve shifted toward the negative potential with nifedipine. On washout of the drugs, the effects of CD-349 or nitrendipine were not readily reversed compared with those of nifedipine. CD-349 had no effect on either inward rectifying (IK1) or delayed outward potassium (IK) or hyperpolarization-activated inward (If) currents. These observations suggest that, in cardiac tissues, CD-349 selectively inhibits the calcium current, presumably by acting on the inactivated channel.
Tsuchida
K
K
Research Center, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Kaneko
K
K
Aihara
H
H
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004594:Electrophysiology; D006041:Goats / Q000502:physiology*; D066298:In Vitro Techniques; D008839:Microelectrodes; D009543:Nifedipine / Q000494:pharmacology; D009568:Nitrendipine / Q000494:pharmacology; D011690:Purkinje Fibers / Q000187:drug effects*
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C054179:CD 349; D009568:Nitrendipine; D009543:Nifedipine