New observations on the mechanisms of antiarrhythmic actions of disopyramide on cardiac membranes.
Electrophysiologic effects of disopyramide on cardiac membranes were studied using the microelectrode technique applied to papillary muscles and the suction pipette whole-cell clamp method applied to isolated ventricular myocytes from guinea-pig hearts. In contrast to previous reports, the development and recovery from the Vmax blocks of action potentials by disopyramide and lidocaine were best expressed by 2 exponential functions, not 1, suggesting that there might be 2 different processes for the sodium current block. A near-therapeutic concentration (11 microM) of disopyramide depressed Vmax at frequencies of 0.1 to 2.0 Hz decreased action potential amplitude and shortened plateau phase in ventricular myocytes. Action potential duration was prolonged by the drug in most of the preparations but shortened in some. Disopyramide prolonged the refractory period and increased threshold current for excitation. The drug was also shown to depress both the calcium current and the delayed outward potassium current. These multiple actions of disopyramide may explain its variety of antiarrhythmic properties.
Hiraoka
M
M
Department of Cardiovascular Diseases, Tokyo Medical and Dental University, Japan.
Kuga
K
K
Kawano
S
S
Sunami
A
A
Fan
Z
Z
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001696:Biomechanical Phenomena; D002462:Cell Membrane / Q000187:drug effects; D004206:Disopyramide / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006352:Heart Ventricles; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000648:ultrastructure; D009994:Osmolar Concentration; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology
D000889:Anti-Arrhythmia Agents; D004206:Disopyramide