Use-dependent block of Ca2+ current by moricizine in guinea-pig ventricular myocytes: a possible ionic mechanism of action potential shortening.
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.
Department of Cardiovascular Diseases, Tokyo Medical and Dental University, Japan.
T
T
Yamane
A
A
Sunami
T
T
Sawanobori
M
M
Hiraoka
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D066298:In Vitro Techniques; D007700:Kinetics; D016293:Moricizine / Q000494:pharmacology*; D009206:Myocardium / Q000166:cytology*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D012996:Solutions
D015220:Calcium Channels; D015221:Potassium Channels; D012996:Solutions; D016293:Moricizine; D012964:Sodium; D002118:Calcium