Effects of cibenzoline, a new class Ia antiarrhythmic drug, on various membrane ionic currents and action potentials of guinea-pig ventricular cells.
We examined the effects of cibenzoline, a new class Ia antiarrhythmic drug, on various membrane ionic currents and action potentials of guinea-pig single ventricular cells, using patch clamp techniques in whole-cell configuration. Action potentials and the membrane currents were evoked at a clamping rate of 0.2 Hz, and all experiments were performed at 32-33 degrees C. 1) Cibenzoline (5, 10 and 30 microM) decreased the Na+ current (INa), in a concentration-dependent manner. The concentration of the half-maximal inhibition (Kd) for INa was estimated to be 7.8 microM. 2) In addition to the inhibition of INa, this drug (5, 10, and 30 microM) decreased, in a concentration-dependent manner, all other membrane currents examined, such as L-type Ca2+ current (ICa), delayed rectifier K+ current (IK), and inward rectifier K+ current (IK1). The Kd (apparent dissociation constant) values were 14.4 microM for ICa, 23.0 microM for IK, and 33.7 microM for IK1 respectively. 3) Cibenzoline (5, 10, and 30 microns) significantly shortened the action potential duration measured at both 30% and 90% repolarization without altering the resting membrane potential. From these findings, we conclude that apart from potent inhibitory effects on INa, cibenzoline possesses multiple blocking effects on other currents, e.g., ICa, IK and IK1, with a different potency (INa > ICa > IK > IK1) and with essentially the same efficacy. These effects may explain, at least in part, the alleged, potent antiarrhythmic effects of this drug.
Sato
T
T
Department of Physiology, Oita Medical University, School of Medicine, Japan.
Wu
B
B
Kiyosue
T
T
Arita
M
M
D000200:Action Potentials / Q000187:drug effects; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects; D015222:Sodium Channels / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D015220:Calcium Channels; D007093:Imidazoles; D007473:Ion Channels; D015221:Potassium Channels; D015222:Sodium Channels; D000255:Adenosine Triphosphate; C032151:cifenline