Biomaterial Database

Electrophysiological effects of AFD-21 and AFD-19, new antiarrhythmic compounds on papillary muscles and single ventricular myocytes isolated from guinea-pig hearts. 1990

I Kodama, and K Kamiya, and T Kawamura, and R Suzuki, and J Toyama

Department of Circulation and Respiration, Nagoya University, Japan.

1. The effects of AFD-21, a newly synthesized antiarrhythmic compound, and AFD-19, its active metabolite, on transmembrane action potentials were examined in right ventricular papillary muscles and single ventricular myocytes isolated from guinea-pig hearts. 2. In papillary muscles, AFD-21 10(-5) M caused a slight prolongation of action potential duration (APD), while AFD-19 above 10(-6) M shortened APD in a dose-dependent manner. 3. Both AFD-21 and AFD-19 above 10(-6) M caused a significant and dose-dependent decrease in the maximum upstroke velocity (Vmax) of the action potential without affecting the resting membrane potential. 4. In the presence of AFD-21 or AFD-19, trains of stimuli at rates greater than or equal to 0.2 Hz led to an exponential decline in Vmax. This use-dependent block was enhanced at higher stimulation frequencies. A time constant for the recovery of Vmax from the use-dependent block was 2.9 s for AFD-21 and 3.6s for AFD-19. 5. The curves relating membrane potential and Vmax were shifted by AFD-21 (10(-5) M), or AFD-19 (10(-5) M) to the direction of more negative potentials by 5.3 mV and 5.1 mV respectively. 6. In single ventricular myocytes treated with AFD-21 (10(-5) M) or AFD-19 (10(-5) M), Vmax of test action potentials preceded by conditioning clamp pulses to 0 mV was decreased progressively as the clamp pulse duration was prolonged. 7. These findings suggest that both AFD-21 and AFD-19 have use- and voltage-dependent inhibitory action on the sodium channel by binding to the channel during its inactivated state, and that the unbinding rate is comparable to that of Class I antiarrhythmic drugs with intermediate kinetics.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008297	Male		Males
D008564	Membrane Potentials	The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).	Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D009206	Myocardium	The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.	Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D010210	Papillary Muscles	Conical muscular projections from the walls of the cardiac ventricles, attached to the cusps of the atrioventricular valves by the chordae tendineae.	Muscle, Papillary,Muscles, Papillary,Papillary Muscle
D005260	Female		Females
D006168	Guinea Pigs	A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.	Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D006321	Heart	The hollow, muscular organ that maintains the circulation of the blood.	Hearts
D000200	Action Potentials	Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.	Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential
D000605	Amino Alcohols	Compounds possessing both a hydroxyl (-OH) and an amino group (-NH2).	Alcohols, Amino