Cardiac electrophysiologic effects of AHR 5360C. 1988

V M Viamonte, and M Hamra, and M R Rosen
Department of Pharmacology, Columbia University, College of Physicians and Surgeons, New York, NY 10032.

We used microelectrode and blood superfusion techniques to study the cardiac electrophysiologic effects of a new drug, AHR 5360C, which has antihypertensive and calcium channel blocking properties in several experimental models. AHR 5360C, 10(-7) M significantly depressed the amplitude of the slow response action potential in canine Purkinje fibers. The fast response action potential was also depressed in a dose-dependent fashion, but with a threshold concentration of 5 X 10(-6) M. AHR 5360C decreased normal automaticity and barium-induced abnormal automaticity at concentrations of 5 X 10(-6) and 10(-5) M respectively, as well as ouabain-induced delayed afterdepolarizations at a threshold concentration of 10(-6) M. In blood superfusion studies; i.v. administration of AHR 5360C, 0.3 mg/kg, significantly reduced blood pressure. Doses of 1.0 mg/kg induced a high degree of A-V block, further reduction of blood pressure, and no physiological changes in heart rate and in the blood superfused fibers. In conclusion, AHR 5360C has calcium blocking properties that depress A-V conduction at concentrations that do not affect the sodium-dependent fast response action potential.

UI MeSH Term Description Entries
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
D008839 Microelectrodes Electrodes with an extremely small tip, used in a voltage clamp or other apparatus to stimulate or record bioelectric potentials of single cells intracellularly or extracellularly. (Dorland, 28th ed) Electrodes, Miniaturized,Electrode, Miniaturized,Microelectrode,Miniaturized Electrode,Miniaturized Electrodes
D010880 Piperidines A family of hexahydropyridines.
D011690 Purkinje Fibers Modified cardiac muscle fibers composing the terminal portion of the heart conduction system. Purkinje Fiber,Fiber, Purkinje,Fibers, Purkinje
D001794 Blood Pressure PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS. Systolic Pressure,Diastolic Pressure,Pulse Pressure,Pressure, Blood,Pressure, Diastolic,Pressure, Pulse,Pressure, Systolic,Pressures, Systolic
D002121 Calcium Channel Blockers A class of drugs that act by selective inhibition of calcium influx through cellular membranes. Calcium Antagonists, Exogenous,Calcium Blockaders, Exogenous,Calcium Channel Antagonist,Calcium Channel Blocker,Calcium Channel Blocking Drug,Calcium Inhibitors, Exogenous,Channel Blockers, Calcium,Exogenous Calcium Blockader,Exogenous Calcium Inhibitor,Calcium Channel Antagonists,Calcium Channel Blocking Drugs,Exogenous Calcium Antagonists,Exogenous Calcium Blockaders,Exogenous Calcium Inhibitors,Antagonist, Calcium Channel,Antagonists, Calcium Channel,Antagonists, Exogenous Calcium,Blockader, Exogenous Calcium,Blocker, Calcium Channel,Blockers, Calcium Channel,Calcium Blockader, Exogenous,Calcium Inhibitor, Exogenous,Channel Antagonist, Calcium,Channel Blocker, Calcium,Inhibitor, Exogenous Calcium
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D004594 Electrophysiology The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
D006321 Heart The hollow, muscular organ that maintains the circulation of the blood. Hearts
D006329 Heart Conduction System An impulse-conducting system composed of modified cardiac muscle, having the power of spontaneous rhythmicity and conduction more highly developed than the rest of the heart. Conduction System, Heart,Conduction Systems, Heart,Heart Conduction Systems,System, Heart Conduction,Systems, Heart Conduction

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