Abstract
1. The effects of imipramine on action potential characteristics and transient outward potassium current (It) of rabbit isolated atrial myocytes were studied using the whole-cell configuration of the patch-clamp technique. 2. Imipramine, 3 microM, decreased action potential amplitude and lengthened the action potential duration measured at 50% of repolarization, whereas it did not modify the final phase of repolarization or the resting membrane potential. These results are similar to those reported in multicellular rabbit atrial preparations. 3. Imipramine, 0.1-100 microM, induced a concentration-dependent inhibition of the peak amplitude of It, a shortening of the time to peak current and an increase in the inactivation rate. The acceleration of the current inactivation is to a major extent responsible for the decrease in the integral of the outward current measured at 50 ms after the start of the pulse. 4. The drug-induced block of It was not associated with changes in the voltage-dependence of the steady-state inactivation curve or in the process of recovery from inactivation of the current. Extrapolation to zero block shows that imipramine did not block It before its activation at the onset of the depolarization. These results suggested that imipramine does not affect the inactivated or the resting state of It channels. 5. It is concluded that in rabbit isolated atrial cells, imipramine inhibits It and that this effect is responsible for the lengthening of the action potential duration produced by this drug.
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- Amsterdam J., Brunswick D., Mendels J. The clinical application of tricyclic antidepressant pharmacokinetics and plasma levels. Am J Psychiatry. 1980 Jun;137(6):653–662. doi: 10.1176/ajp.137.6.653. [DOI] [PubMed] [Google Scholar]
- Castle N. A. Bupivacaine inhibits the transient outward K+ current but not the inward rectifier in rat ventricular myocytes. J Pharmacol Exp Ther. 1990 Dec;255(3):1038–1046. [PubMed] [Google Scholar]
- Castle N. A. Selective inhibition of potassium currents in rat ventricle by clofilium and its tertiary homolog. J Pharmacol Exp Ther. 1991 Apr;257(1):342–350. [PubMed] [Google Scholar]
- Clark R. B., Giles W. R., Imaizumi Y. Properties of the transient outward current in rabbit atrial cells. J Physiol. 1988 Nov;405:147–168. doi: 10.1113/jphysiol.1988.sp017326. [DOI] [PMC free article] [PubMed] [Google Scholar]
- De Jalon P. G., Rodriguez S. M., Tamargo J. Electrophysiological effects of imipramine in guinea pig-myocardium [proceedings]. Br J Pharmacol. 1978 Jun;63(2):373P–373P. [PMC free article] [PubMed] [Google Scholar]
- Delpón E., Tamargo J., Sánchez-Chapula J. Further characterization of the effects of imipramine on plateau membrane currents in guinea-pig ventricular myocytes. Naunyn Schmiedebergs Arch Pharmacol. 1991 Dec;344(6):645–652. doi: 10.1007/BF00174748. [DOI] [PubMed] [Google Scholar]
- Delpón E., Valenzuela C., Tamargo J. Tonic and frequency-dependent Vmax block induced by imipramine in guinea pig ventricular muscle fibers. J Cardiovasc Pharmacol. 1990 Mar;15(3):414–420. doi: 10.1097/00005344-199003000-00011. [DOI] [PubMed] [Google Scholar]
- Dukes I. D., Cleemann L., Morad M. Tedisamil blocks the transient and delayed rectifier K+ currents in mammalian cardiac and glial cells. J Pharmacol Exp Ther. 1990 Aug;254(2):560–569. [PubMed] [Google Scholar]
- Elonen E., Linnoila M., Lukkari I., Mattila M. J. Concentration of tricyclic antidepressants in plasma, heart and skeletal muscle after their intravenous infusion to anaesthetized rabbits. Acta Pharmacol Toxicol (Copenh) 1975 Oct;37(4):274–281. doi: 10.1111/j.1600-0773.1975.tb00845.x. [DOI] [PubMed] [Google Scholar]
- Escande D., Coulombe A., Faivre J. F., Deroubaix E., Coraboeuf E. Two types of transient outward currents in adult human atrial cells. Am J Physiol. 1987 Jan;252(1 Pt 2):H142–H148. doi: 10.1152/ajpheart.1987.252.1.H142. [DOI] [PubMed] [Google Scholar]
- Giles W. R., Imaizumi Y. Comparison of potassium currents in rabbit atrial and ventricular cells. J Physiol. 1988 Nov;405:123–145. doi: 10.1113/jphysiol.1988.sp017325. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Glassman A. H., Perel J. M. The clinical pharmacology of imipramine. Implications for therapeutics. Arch Gen Psychiatry. 1973 May;28(5):649–653. doi: 10.1001/archpsyc.1973.01750350029006. [DOI] [PubMed] [Google Scholar]
- Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
- Hume J. R., Giles W. Ionic currents in single isolated bullfrog atrial cells. J Gen Physiol. 1983 Feb;81(2):153–194. doi: 10.1085/jgp.81.2.153. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hume J. R., Uehara A. Ionic basis of the different action potential configurations of single guinea-pig atrial and ventricular myocytes. J Physiol. 1985 Nov;368:525–544. doi: 10.1113/jphysiol.1985.sp015874. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Imaizumi Y., Giles W. R. Quinidine-induced inhibition of transient outward current in cardiac muscle. Am J Physiol. 1987 Sep;253(3 Pt 2):H704–H708. doi: 10.1152/ajpheart.1987.253.3.H704. [DOI] [PubMed] [Google Scholar]
- Isenberg G., Klockner U. Calcium tolerant ventricular myocytes prepared by preincubation in a "KB medium". Pflugers Arch. 1982 Oct;395(1):6–18. doi: 10.1007/BF00584963. [DOI] [PubMed] [Google Scholar]
- Isenberg G., Tamargo J. Effect of imipramine on calcium and potassium currents in isolated bovine ventricular myocytes. Eur J Pharmacol. 1985 Jan 22;108(2):121–131. doi: 10.1016/0014-2999(85)90716-2. [DOI] [PubMed] [Google Scholar]
- Jandhyala B. S., Steenberg M. L., Perel J. M., Manian A. A., Buckley J. P. Effects of several tricyclic antidepressants on the hemodynamics and myocardial contractility of the anesthetized dogs. Eur J Pharmacol. 1977 Apr 21;42(4):403–410. doi: 10.1016/0014-2999(77)90175-3. [DOI] [PubMed] [Google Scholar]
- Josephson I. R., Sanchez-Chapula J., Brown A. M. Early outward current in rat single ventricular cells. Circ Res. 1984 Feb;54(2):157–162. doi: 10.1161/01.res.54.2.157. [DOI] [PubMed] [Google Scholar]
- Manzanares J., Tamargo J. Electrophysiological effects of imipramine in nontreated and in imipramine-pretreated rat atrial fibres. Br J Pharmacol. 1983 May;79(1):167–175. doi: 10.1111/j.1476-5381.1983.tb10509.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marshall J. B., Forker A. D. Cardiovascular effects of tricyclic antidepressant drugs: therapeutic usage, overdose, and management of complications. Am Heart J. 1982 Mar;103(3):401–414. doi: 10.1016/0002-8703(82)90281-2. [DOI] [PubMed] [Google Scholar]
- Matsuo S. Comparative effects of imipramine and propranolol on the transmembrane potentials of the isolated rabbit atria. Jpn J Pharmacol. 1967 Jun;17(2):279–286. doi: 10.1254/jjp.17.279. [DOI] [PubMed] [Google Scholar]
- Ogata N., Narahashi T. Block of sodium channels by psychotropic drugs in single guinea-pig cardiac myocytes. Br J Pharmacol. 1989 Jul;97(3):905–913. doi: 10.1111/j.1476-5381.1989.tb12031.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rawling D. A., Fozzard H. A. Effects of imipramine on cellular electrophysiological properties of cardiac Purkinje fibers. J Pharmacol Exp Ther. 1979 Jun;209(3):371–375. [PubMed] [Google Scholar]
- Rodriguez S., Tamargo J. Electrophysiological effects of imipramine on bovine ventricular muscle and Purkinje fibres. Br J Pharmacol. 1980 Sep;70(1):15–23. doi: 10.1111/j.1476-5381.1980.tb10899.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shibata E. F., Drury T., Refsum H., Aldrete V., Giles W. Contributions of a transient outward current to repolarization in human atrium. Am J Physiol. 1989 Dec;257(6 Pt 2):H1773–H1781. doi: 10.1152/ajpheart.1989.257.6.H1773. [DOI] [PubMed] [Google Scholar]
- Sánchez-Chapula J. Effects of bupivacaine on membrane currents of guinea-pig ventricular myocytes. Eur J Pharmacol. 1988 Nov 8;156(3):303–308. doi: 10.1016/0014-2999(88)90274-9. [DOI] [PubMed] [Google Scholar]
- Vaughan Williams E. M. A classification of antiarrhythmic actions reassessed after a decade of new drugs. J Clin Pharmacol. 1984 Apr;24(4):129–147. doi: 10.1002/j.1552-4604.1984.tb01822.x. [DOI] [PubMed] [Google Scholar]
- Wallenstein S., Zucker C. L., Fleiss J. L. Some statistical methods useful in circulation research. Circ Res. 1980 Jul;47(1):1–9. doi: 10.1161/01.res.47.1.1. [DOI] [PubMed] [Google Scholar]