Electrophysiological effects of the tricyclic antidepressant desipramine on mammalian myocardium.
Effects of desipramine (DPr), a tricyclic antidepressant, on isolated trabeculae of the right rabbit atrial myocardium were studied using a standard microelectrode technique. Between 10(-7) and 10(-4) g/ml DPr reduced the maximum upstroke velocity Vmax of the action potentials. The membrane responsiveness was found to be depressed for DPr increased the time constant of the recovery of Vmax in a concentration-dependent manner distinctly. The voltage-Vmax relationships were shifted to more positive potentials and were flattend by increasing the concentration of DPr. DPr prolonged the duration of the action potentials on all levels of repolarization. Between 10(-7) and 10(-5) g/ml both resting and overshoot potential were found to be unchanged. At concentrations higher than 10(-5) g/ml slow response action potential insensitive to 10(-5) mol/l TTX were evoked, the resting transmembrane potential depolarized, spatial inhomogeneities in transmembrane potential and triggered activity could be observed. DPr may act antiarrhythmogenically in a quinidine-like manner at concentrations between 10(-7) and 10(-5) g/ml by (1) decreasing the fast channel conductance, (2) delaying the recovery of the fast channel. At concentrations higher than 10(-5) g/ml DPr could effect arrhythmogenic actions by a complete depression of fast response action potentials, unmasking of slow response action potentials and generation of severe spatial inhomogeneities.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D016275:Atrial Function; D002462:Cell Membrane / Q000502:physiology; D003891:Desipramine / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D011817:Rabbits; D013779:Tetrodotoxin / Q000494:pharmacology
D013779:Tetrodotoxin; D003891:Desipramine