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. 1983 Nov;80(3):511–517. doi: 10.1111/j.1476-5381.1983.tb10723.x

Effects of amrinone on the transmembrane action potential of rabbit sinus node pacemaker cells.

I Kodama, N Kondo, S Shibata
PMCID: PMC2045008  PMID: 6640204

Abstract

Effects of amrinone on the membrane action potential and spontaneous activity were investigated in sinus node pacemaker cells of rabbit heart by use of microelectrode techniques. Amrinone (1 X 10(-4) M to 6 X 10(-6) M) caused a shortening of cycle length of spontaneous firing (SPCL) accompanied by an increase in the maximum upstroke velocity at phase O (Vmax) and amplitude of action potential (AAP), while it did not affect the maximum diastolic potential (MDP). All the effects of amrinone on sinus node pacemaker cells were markedly attenuated or abolished in a low calcium medium (Ca+ 0.1 mM or 0.3 mM) or in the presence of the slow channel blocking agent, verapamil (5 X 10(-7) M, 2 X 10(-6) M). The effects of amrinone were not antagonized by the beta-adrenoceptor blocking agent, pindolol (2 X 10(-7) M). These results indicate that amrinone has an intrinsic effect on sinus node pacemaker cells, increasing their spontaneous firing activity. It is also assumed that the effects of amrinone on sinus node cells are probably mediated by an augmentation of the slow calcium and/or sodium inward current through the cell membrane.

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Selected References

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  1. Adams H. R., Rhody J., Sutko J. L. Amrinone activates K+-depolarized atrial and ventricular myocardium of guinea pigs. Circ Res. 1982 Nov;51(5):662–665. doi: 10.1161/01.res.51.5.662. [DOI] [PubMed] [Google Scholar]
  2. Benotti J. R., Grossman W., Braunwald E., Carabello B. A. Effects of amrinone on myocardial energy metabolism and hemodynamics in patients with severe congestive heart failure due to coronary artery disease. Circulation. 1980 Jul;62(1):28–34. doi: 10.1161/01.cir.62.1.28. [DOI] [PubMed] [Google Scholar]
  3. Farah A. E., Alousi A. A. New cardiotonic agents: a search for digitalis substitute. Life Sci. 1978 Apr 3;22(13-15):1139–1147. doi: 10.1016/0024-3205(78)90083-8. [DOI] [PubMed] [Google Scholar]
  4. Hariman R. J., Hoffman B. F. Effects of ouabain and vagal stimulation on sinus nodal function in conscious dogs. Circ Res. 1982 Dec;51(6):760–768. doi: 10.1161/01.res.51.6.760. [DOI] [PubMed] [Google Scholar]
  5. Honerjäger P., Schäfer-Korting M., Reiter M. Involvement of cyclic AMP in the direct inotropic action of amrinone. Biochemical and functional evidence. Naunyn Schmiedebergs Arch Pharmacol. 1981 Dec;318(2):112–120. doi: 10.1007/BF00508835. [DOI] [PubMed] [Google Scholar]
  6. Irisawa H. Comparative physiology of the cardiac pacemaker mechanism. Physiol Rev. 1978 Apr;58(2):461–498. doi: 10.1152/physrev.1978.58.2.461. [DOI] [PubMed] [Google Scholar]
  7. LeJemtel T. H., Keung E., Sonnenblick E. H., Ribner H. S., Matsumoto M., Davis R., Schwartz W., Alousi A. A., Davolos D. Amrinone: a new non-glycosidic, non-adrenergic cardiotonic agent effective in the treatment of intractable myocardial failure in man. Circulation. 1979 Jun;59(6):1098–1104. doi: 10.1161/01.cir.59.6.1098. [DOI] [PubMed] [Google Scholar]
  8. Li T., Sperelakis N. Stimulation of slow action potentials in guinea pig papillary muscle cells by intracellular injection of cAMP, Gpp(NH)p, and cholera toxin. Circ Res. 1983 Jan;52(1):111–117. doi: 10.1161/01.res.52.1.111. [DOI] [PubMed] [Google Scholar]
  9. Noma A., Irisawa H. Effects of calcium ion on the rising phase of the action potential in rabbit sinoatrial node cells. Jpn J Physiol. 1976;26(1):93–99. doi: 10.2170/jjphysiol.26.93. [DOI] [PubMed] [Google Scholar]
  10. Noma A., Kotake H., Irisawa H. Slow inward current and its role mediating the chronotropic effect of epinephrine in the rabbit sinoatrial node. Pflugers Arch. 1980 Oct;388(1):1–9. doi: 10.1007/BF00582621. [DOI] [PubMed] [Google Scholar]
  11. Noma A., Yanagihara K., Irisawa H. Inward current of the rabbit sinoatrial node cell. Pflugers Arch. 1977 Nov 25;372(1):43–51. doi: 10.1007/BF00582205. [DOI] [PubMed] [Google Scholar]
  12. Onuaguluchi G., Tanz R. D. Cardiac effects of amrinone on rabbit papillary muscle and guinea pig Langendorff heart preparations. J Cardiovasc Pharmacol. 1981 Nov-Dec;3(6):1342–1355. doi: 10.1097/00005344-198111000-00022. [DOI] [PubMed] [Google Scholar]
  13. Shimizu T., Iwamura N., Kodama I., Toyama J., Yamada K. Effects of beta-adrenergic blocking drug pindolol (LB46) on cardiac fibers in relation to its membrane effects. Jpn Heart J. 1978 Nov;19(6):865–876. doi: 10.1536/ihj.19.865. [DOI] [PubMed] [Google Scholar]
  14. Singh B. N., Williams E. M. Effects on cardiac muscle of the -adrenoceptor blocking drugs INPEA and LB46 in relation to their local anaesthetic action on nerve. Br J Pharmacol. 1971 Sep;43(1):10–22. doi: 10.1111/j.1476-5381.1971.tb07152.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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