Use‐dependent block of Ca2+ current by moricizine in guinea‐pig ventricular myocytes: a possible ionic mechanism of action potential shortening

• Published in: British journal of pharmacology 1993-03, Vol.108 (3), p.812-818
• Main Authors: Yamane, Tei‐ichi, Sunami, Akihiko, Sawanobori, Tohru, Hiraoka, Masayasu
• Format: Article
• Language: English
• Subjects: action potential duration; Action Potentials - drug effects; Animals; Antiarythmic agents; Biological and medical sciences; Calcium - metabolism; Calcium Channels - drug effects; Cardiovascular system; Guinea Pigs; guinea‐pig ventricular myocytes; Heart - drug effects; Heart Ventricles - cytology; Heart Ventricles - drug effects; In Vitro Techniques; Kinetics; Medical sciences; Moricizine; Moricizine - pharmacology; Myocardium - cytology; Pharmacology. Drug treatments; Potassium Channels - drug effects; Potassium Channels - metabolism; Sodium - metabolism; Solutions; use‐dependent block of Ca2+ current
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1993.tb12883.x

1 Whole cell patch clamp techniques were used to study the effects of moricizine on membrane currents in guinea‐pig ventricular myocytes. 2 Application of moricizine caused reversible depression of the time‐dependent outward K+ current. 3 The Na+/Ca2+ exchange current was not directly affected by moricizine. 4 Although moricizine hardly affected the L‐type Ca2+ current when cells were stimulated at a frequency of 0.1 Hz, it suppressed the current at depolarized holding potentials in a use‐dependent manner at 1 Hz. 5 Developments of use‐dependent block of the Ca2+ current in the presence of moricizine were best expressed by two exponentials. Binding to both activated and inactivated states of the Ca2+ channel were supported from the binding kinetics study. 6 We concluded that moricizine suppressed the L‐type Ca2+ current in a use‐dependent manner and this might explain, at least in part, action potential shortening by the drug.