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. 1979 Sep;294:255–277. doi: 10.1113/jphysiol.1979.sp012929

Inotropic and arrhythmogenic effects of potassium-depleted solutions on mammalian cardiac muscle.

D A Eisner, W J Lederer
PMCID: PMC1280556  PMID: 512946

Abstract

1. We have investigated the electrical and mechanical effects of reducing the bathing K concentration, K0, over the range from 4-0 mM in guinea-pig papillary muscle and in sheep Purkinje fibres. 2. In papillary muscle, reducing K0 to zero produces a negative shift in the resting potential and an initial increase in action potential duration. An increase of twitch tension ensues, followed by a reduction in actin potential duration and, eventually, an increase in tonic tension. This increase in tonic tension is often accompanied by a decrease of twitch tension. Finally, transient depolarizations and after contractions are produced. 3. In voltage clamped Purkinje fibres, K0 reduction decreases the slope conductance at the more negative potentials and reduces the pace-maker current, iK2. Twitch tension increases rapidly and voltage dependent tonic tension develops. After even very short exposures to very low K0 (1 mM and below), an oscillatory transient inward current and accompanying aftercontraction can be seen. The oscillatory transient inward current and aftercontraction are similar to those described for cardiotonic steroid intoxication by Kass, Lederer, Tsien & Weingart (1978). 4. Prolonged exposure to 0 K0 leads to the development of a slow current 'creep'. This current is activated by depolarization and has a reversal potential of -6.7 +/- 3.5 mV. The development of this creep current is accompanied by an increasing 'creep' in tonic tension with the same time course. On repolarization both the current creep and creep in tension recover with time courses still similar to each other. 5. Fluctuations appear in both the tension and current records during exposure to low K0. The tension and current fluctuations have similar principal frequencies (about 1 Hz). 6. Ca0 removal, substituting Ba0 for Ca0 or adding Mn0 (2 mM) can each remove the transient inward current, aftercontraction, fluctuations of current and tension, and creep current as well as the increase of twitch and tonic tension. 7. Replacing Ca0 by Sr0 leads to an increased inotropic effect of low K0 with altered kinetics and appears to abolish the transient inward current, aftercontraction and fluctuations of current and tension. 8. It is concluded that Ca1 plays a central role in the inotropic and arrhythmogenic effects of low K0. Possible mechanisms of Ca1 control are discussed in light of the results that have been presented.

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Selected References

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  1. Baker P. F., McNaughton P. A. The effect of membrane potential on the calcium transport systems in squid axons [proceedings]. J Physiol. 1976 Sep;260(2):24P–25P. [PubMed] [Google Scholar]
  2. Bass B. G., Ciulla E. M., Klop P., Van Baal S. Some electrical and mechanical effects of strontium on toad ventricular muscle: comparison to calcium. J Physiol. 1975 Nov;252(3):547–564. doi: 10.1113/jphysiol.1975.sp011158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baumgarten C. M., Isenberg G. Depletion and accumulation of potassium in the extracellular clefts of cardiac Purkinje fibers during voltage clamp hyperpolarization and depolarization. Pflugers Arch. 1977 Mar 11;368(1-2):19–31. doi: 10.1007/BF01063450. [DOI] [PubMed] [Google Scholar]
  4. Busselen P., van Kerkhove E. The effect of sodium, calcium and metabolic inhibitors on calcium efflux from goldfish heart ventricles. J Physiol. 1978 Sep;282:263–283. doi: 10.1113/jphysiol.1978.sp012462. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. DECK K. A., KERN R., TRAUTWEIN W. VOLTAGE CLAMP TECHNIQUE IN MAMMALIAN CARDIAC FIBRES. Pflugers Arch Gesamte Physiol Menschen Tiere. 1964 Jun 9;280:50–62. doi: 10.1007/BF00412615. [DOI] [PubMed] [Google Scholar]
  6. Davidson S., Surawicz B. Ectopic beats and atrioventricular conduction disturbances. In patients with hypopotassemia. Arch Intern Med. 1967 Sep;120(3):280–285. [PubMed] [Google Scholar]
  7. Deitmer J. W., Ellis D. Changes in the intracellular sodium activity of sheep heart Purkinje fibres produced by calcium and other divalent cations. J Physiol. 1978 Apr;277:437–453. doi: 10.1113/jphysiol.1978.sp012283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dudel J., Peper K., Rüdel R., Trautwein W. The potassium component of membrane current in Purkinje fibers. Pflugers Arch Gesamte Physiol Menschen Tiere. 1967;296(4):308–327. doi: 10.1007/BF00362531. [DOI] [PubMed] [Google Scholar]
  9. Ebashi S., Kodama A., Ebashi F. Troponin. I. Preparation and physiological function. J Biochem. 1968 Oct;64(4):465–477. doi: 10.1093/oxfordjournals.jbchem.a128918. [DOI] [PubMed] [Google Scholar]
  10. Ehara T. Late potentiating effect of low-K ringer solution on the contractility of the bullfrog ventricle. Jpn J Physiol. 1974 Jun;24(3):329–342. doi: 10.2170/jjphysiol.24.329. [DOI] [PubMed] [Google Scholar]
  11. Eisner D. A., Lederer W. J., Ojeda C. Arrhythmogenic effects of hypokalaemia on mammalian ventricular muscle [proceedings]. J Physiol. 1978 Jul;280:74P–75P. [PubMed] [Google Scholar]
  12. Eisner D. A., Lederer W. J. The role of the sodium pump in the effects of potassium-depleted solutions on mammalian cardiac muscle. J Physiol. 1979 Sep;294:279–301. doi: 10.1113/jphysiol.1979.sp012930. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ellis D. The effects of external cations and ouabain on the intracellular sodium activity of sheep heart Purkinje fibres. J Physiol. 1977 Dec;273(1):211–240. doi: 10.1113/jphysiol.1977.sp012090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ferrier G. R., Moe G. K. Effect of calcium on acetylstrophanthidin-induced transient depolarizations in canine Purkinje tissue. Circ Res. 1973 Nov;33(5):508–515. doi: 10.1161/01.res.33.5.508. [DOI] [PubMed] [Google Scholar]
  15. Ferrier G. R. The effects of tension on acetylstrophanthidin-induced transient depolarizations and aftercontractions in canine myocardial and Purkinje tissues. Circ Res. 1976 Mar;38(3):156–162. doi: 10.1161/01.res.38.3.156. [DOI] [PubMed] [Google Scholar]
  16. Fozzard H. A., Hellman D. C. Relationship between membrane voltage and tension in voltage-clamped cardiac purkinje fibres. Nature. 1968 May 11;218(5141):588–589. doi: 10.1038/218588a0. [DOI] [PubMed] [Google Scholar]
  17. GLYNN I. M. The action of cardiac glycosides on sodium and potassium movements in human red cells. J Physiol. 1957 Apr 3;136(1):148–173. doi: 10.1113/jphysiol.1957.sp005749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gibbons W. R., Fozzard H. A. Voltage dependence and time dependence of contraction in sheep cardiac Purkinje fibers. Circ Res. 1971 Apr;28(4):446–460. doi: 10.1161/01.res.28.4.446. [DOI] [PubMed] [Google Scholar]
  19. Goto M., Tsuda Y., Yatani A. Two mechanisms for positive inotropism of low-K Ringer solution in bullfrog atrium. Nature. 1977 Aug 25;268(5622):755–757. doi: 10.1038/268755a0. [DOI] [PubMed] [Google Scholar]
  20. Hauswirth O., Noble D., Tsien R. W. The mechanism of oscillatory activity at low membrane potentials in cardiac Purkinje fibres. J Physiol. 1969 Jan;200(1):255–265. doi: 10.1113/jphysiol.1969.sp008691. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Horackova M., Vassort G. Proceedings: Regulation of tonic tension in frog atrial muscle by voltage-dependent Na-Ca exchange. J Physiol. 1976 Jun;258(2):77P–78P. [PubMed] [Google Scholar]
  22. Isenberg G., Trautwein W. The effect of dihydro-ouabain and lithium-ions on the outward current in cardiac Purkinje fibers. Evidence for electrogenicity of active transport. Pflugers Arch. 1974;350(1):41–54. doi: 10.1007/BF00586737. [DOI] [PubMed] [Google Scholar]
  23. Jundt H., Porzig H., Reuter H., Stucki J. W. The effect of substances releasing intracellular calcium ions on sodium-dependent calcium efflux from guinea-pig auricles. J Physiol. 1975 Mar;246(1):229–253. doi: 10.1113/jphysiol.1975.sp010888. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kass R. S., Lederer W. J., Tsien R. W., Weingart R. Role of calcium ions in transient inward currents and aftercontractions induced by strophanthidin in cardiac Purkinje fibres. J Physiol. 1978 Aug;281:187–208. doi: 10.1113/jphysiol.1978.sp012416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kass R. S., Siegelbaum S., Tsien R. W. Incomplete inactivation of the slow inward current in cardiac Purkinje fibres [proceedings]. J Physiol. 1976 Dec;263(1):127P–128P. [PubMed] [Google Scholar]
  26. Kass R. S., Tsien R. W. Multiple effects of calcium antagonists on plateau currents in cardiac Purkinje fibers. J Gen Physiol. 1975 Aug;66(2):169–192. doi: 10.1085/jgp.66.2.169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Kohlhardt M., Haastert H. P., Krause H. Evidence of non-specificity of the Ca channel in mammalian myocardial fibre membranes. Substitution of Ca by Sr, Ba or Mg as charge carriers. Pflugers Arch. 1973 Aug 17;342(2):125–136. doi: 10.1007/BF00587843. [DOI] [PubMed] [Google Scholar]
  28. Lederer W. J., Tsien R. W. Proceedings: Transient inward current underlying strophanthidin's enhancement of pace-maker activity in Purkinje fibres. J Physiol. 1975 Jul;249(1):40P–41P. [PubMed] [Google Scholar]
  29. Lederer W. J., Tsien R. W. Transient inward current underlying arrhythmogenic effects of cardiotonic steroids in Purkinje fibres. J Physiol. 1976 Dec;263(2):73–100. doi: 10.1113/jphysiol.1976.sp011622. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Léoty C., Raymond G. Mechanical activity and ionic currents in frog atrial trabeculae. Pflugers Arch. 1972;334(2):114–128. doi: 10.1007/BF00586785. [DOI] [PubMed] [Google Scholar]
  31. McAllister R. E., Noble D. The time and voltage dependence of the slow outward current in cardiac Purkinje fibres. J Physiol. 1966 Oct;186(3):632–662. doi: 10.1113/jphysiol.1966.sp008060. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. McAllister R. E., Noble D., Tsien R. W. Reconstruction of the electrical activity of cardiac Purkinje fibres. J Physiol. 1975 Sep;251(1):1–59. doi: 10.1113/jphysiol.1975.sp011080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Mermier P., Hasselbach W. Comparison between strontium and calcium uptake by the fragmented sarcoplasmic reticulum. Eur J Biochem. 1976 Oct 1;69(1):79–86. doi: 10.1111/j.1432-1033.1976.tb10860.x. [DOI] [PubMed] [Google Scholar]
  34. Noble D., Tsien R. W. The kinetics and rectifier properties of the slow potassium current in cardiac Purkinje fibres. J Physiol. 1968 Mar;195(1):185–214. doi: 10.1113/jphysiol.1968.sp008454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Ochi R. Electrical uncoupling by Sr action potentials in cardiac muscle. Experientia. 1977 Sep 15;33(9):1187–1189. doi: 10.1007/BF01922319. [DOI] [PubMed] [Google Scholar]
  36. Ochi R., Trautwein W. The dependence of cardiac contraction on depolarization and slow inward current. Pflugers Arch. 1971;323(3):187–203. doi: 10.1007/BF00586383. [DOI] [PubMed] [Google Scholar]
  37. Reiter M., Seibel K., Stickel F. J. Sodium dependence of the inotropic effect of a reduction in extracellular potassium concentration. Naunyn Schmiedebergs Arch Pharmakol. 1971;268(4):361–378. doi: 10.1007/BF00997062. [DOI] [PubMed] [Google Scholar]
  38. Reuter H. Divalent cations as charge carriers in excitable membranes. Prog Biophys Mol Biol. 1973;26:1–43. doi: 10.1016/0079-6107(73)90016-3. [DOI] [PubMed] [Google Scholar]
  39. Ringer S. A further Contribution regarding the influence of the different Constituents of the Blood on the Contraction of the Heart. J Physiol. 1883 Jan;4(1):29–42.3. doi: 10.1113/jphysiol.1883.sp000120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Rosen M. R., Gelband H., Merker C., Hoffman B. F. Mechanisms of digitalis toxicity. Effects of ouabain on phase four of canine Purkinje fiber transmembrane potentials. Circulation. 1973 Apr;47(4):681–689. doi: 10.1161/01.cir.47.4.681. [DOI] [PubMed] [Google Scholar]
  41. Rougier O., Vassort G., Garnier D., Gargouil Y. M., Coraboeuf E. Existence and role of a slow inward current during the frog atrial action potential. Pflugers Arch. 1969;308(2):91–110. doi: 10.1007/BF00587018. [DOI] [PubMed] [Google Scholar]
  42. VASSALLE M. CARDIAC PACEMAKER POTENTIALS AT DIFFERENT EXTRA-AND INTRACELLULAR K CONCENTRATIONS. Am J Physiol. 1965 Apr;208:770–775. doi: 10.1152/ajplegacy.1965.208.4.770. [DOI] [PubMed] [Google Scholar]
  43. Vassort G., Rougier O. Membrane potential and slow inward current dependence of frog cardiac mechanical activity. Pflugers Arch. 1972;331(3):191–203. doi: 10.1007/BF00589126. [DOI] [PubMed] [Google Scholar]
  44. Wood E. H., Heppner R. L., Weidmann S. Inotropic effects of electric currents. I. Positive and negative effects of constant electric currents or current pulses applied during cardiac action potentials. II. Hypotheses: calcium movements, excitation-contraction coupling and inotropic effects. Circ Res. 1969 Mar;24(3):409–445. doi: 10.1161/01.res.24.3.409. [DOI] [PubMed] [Google Scholar]

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