Biomaterial Database

Rate-dependent effects of sematilide on action potential duration in isolated guinea pig ventricular myocytes. 1994

T Sawanobori, and H Adaniya, and T Namiki, and M Hiraoka

Department of Cardiovascular Diseases, Tokyo Medical and Dental University, Japan.

We examined the underlying mechanism for rate-dependent effects of sematilide on action potential duration (APD) in guinea pig ventricular myocytes. Sematilide at 10 microM or higher concentrations caused prolongation of the APD without changing other electrical parameters at a stimulation rate of 0.2 Hz. Although 30 microM sematilide significantly prolonged APD by 20 to 40% at 0.2 Hz, the drug-induced prolongation became non-significant at 2.5 Hz, exhibiting a reverse use-dependent effect. Sematilide depressed the delayed outward K+ current (IK) without affecting the inward rectifier K+ current and the L-type Ca++ current. Suppression of IK by sematilide was more prominent on the tail current elicited by short pulses than on those elicited by long pulses, suggesting that its main action was on the rapidly activating component of IK. Sematilide was shown to have an affinity to the rested state of the IK channel, because the inhibition was increased with prolongation of diastolic intervals at -80 mV. Rapid-rate depolarizations induced a transient outward current that was abolished by 5 mM caffeine. This caffeine-sensitive transient outward current could contribute to the shortening of the APD at rapid pulsation, but sematilide had no effects on this current. Therefore, we conclude that sematilide principally blocked the rapidly activating component of IK with affinity for the rested state of the IK channel and did not block the slowly activating component. Also the drug did not affect the caffeine-sensitive transient outward current during rapid-rate depolarizations. All of these factors may contribute to reverse use-dependent effects on action potential prolongation by sematilide.

UI	MeSH Term	Description	Entries
D011342	Procainamide	A class Ia antiarrhythmic drug that is structurally-related to PROCAINE.	Procaine Amide,Apo-Procainamide,Biocoryl,Novocainamide,Novocamid,Procainamide Hydrochloride,Procamide,Procan,Procan SR,Procanbid,Pronestyl,Rhythmin,Amide, Procaine,Hydrochloride, Procainamide
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
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000889	Anti-Arrhythmia Agents	Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade.	Anti-Arrhythmia Agent,Anti-Arrhythmia Drug,Anti-Arrhythmic,Antiarrhythmia Agent,Antiarrhythmia Drug,Antiarrhythmic Drug,Antifibrillatory Agent,Antifibrillatory Agents,Cardiac Depressant,Cardiac Depressants,Myocardial Depressant,Myocardial Depressants,Anti-Arrhythmia Drugs,Anti-Arrhythmics,Antiarrhythmia Agents,Antiarrhythmia Drugs,Antiarrhythmic Drugs,Agent, Anti-Arrhythmia,Agent, Antiarrhythmia,Agent, Antifibrillatory,Agents, Anti-Arrhythmia,Agents, Antiarrhythmia,Agents, Antifibrillatory,Anti Arrhythmia Agent,Anti Arrhythmia Agents,Anti Arrhythmia Drug,Anti Arrhythmia Drugs,Anti Arrhythmic,Anti Arrhythmics,Depressant, Cardiac,Depressant, Myocardial,Depressants, Cardiac,Depressants, Myocardial,Drug, Anti-Arrhythmia,Drug, Antiarrhythmia,Drug, Antiarrhythmic,Drugs, Anti-Arrhythmia,Drugs, Antiarrhythmia,Drugs, Antiarrhythmic
D013997	Time Factors	Elements of limited time intervals, contributing to particular results or situations.	Time Series,Factor, Time,Time Factor
D015221	Potassium Channels	Cell membrane glycoproteins that are selectively permeable to potassium ions. At least eight major groups of K channels exist and they are made up of dozens of different subunits.	Ion Channels, Potassium,Ion Channel, Potassium,Potassium Channel,Potassium Ion Channels,Channel, Potassium,Channel, Potassium Ion,Channels, Potassium,Channels, Potassium Ion,Potassium Ion Channel
D066298	In Vitro Techniques	Methods to study reactions or processes taking place in an artificial environment outside the living organism.	In Vitro Test,In Vitro Testing,In Vitro Tests,In Vitro as Topic,In Vitro,In Vitro Technique,In Vitro Testings,Technique, In Vitro,Techniques, In Vitro,Test, In Vitro,Testing, In Vitro,Testings, In Vitro,Tests, In Vitro,Vitro Testing, In