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. 1988 Jun;94(2):500–508. doi: 10.1111/j.1476-5381.1988.tb11553.x

Effects of halothane on membrane currents associated with contraction in single myocytes isolated from guinea-pig ventricle.

D A Terrar 1, J G Victory 1
PMCID: PMC1854001  PMID: 3395788

Abstract

1. The effects of halothane on electrical activity and contraction were investigated in single myocytes isolated from guinea-pig ventricle. 2. Halothane depressed the plateau and shortened the duration of action potentials. 3. Halothane also reduced the amplitude of inward calcium currents and of additional inward current activated by cytosolic calcium under voltage-clamp conditions. 4. Contractions (measured by an optical technique) accompanying either action potentials or calcium currents were reduced by halothane. However, the extent of attenuation of contraction was greater than when a similar level of calcium channel blockade was induced by application of verapamil. 5. Actions of halothane on calcium-activated tail currents in double-pulse experiments were consistent with reduction by halothane of the cytosolic calcium transient, perhaps as a consequence of reduced uptake of calcium into sarcoplasmic reticulum stores. 6. It is concluded that the actions of halothane on inward currents contribute to its effects on action potentials. The reduction in contraction caused by halothane may result partly from a reduced influx of calcium to trigger contraction, and partly by a reduced release of calcium from sarcoplasmic reticulum stores.

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Selected References

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  1. Blanck T. J., Thompson M. Calcium transport by cardiac sarcoplasmic reticulum: modulation of halothane action by substrate concentration and pH. Anesth Analg. 1981 Jun;60(6):390–394. [PubMed] [Google Scholar]
  2. Bosnjak Z. J., Kampine J. P. Effects of halothane on transmembrane potentials, Ca2+ transients, and papillary muscle tension in the cat. Am J Physiol. 1986 Aug;251(2 Pt 2):H374–H381. doi: 10.1152/ajpheart.1986.251.2.H374. [DOI] [PubMed] [Google Scholar]
  3. Bosnjak Z. J., Kampine J. P. Effects of halothane, enflurane, and isoflurane on the SA node. Anesthesiology. 1983 Apr;58(4):314–321. doi: 10.1097/00000542-198304000-00003. [DOI] [PubMed] [Google Scholar]
  4. Brown B. R., Jr, Crout J. R. A comparative study of the effects of five general anesthetics on myocardial contractility. I. Isometric conditions. Anesthesiology. 1971 Mar;34(3):236–245. doi: 10.1097/00000542-197103000-00007. [DOI] [PubMed] [Google Scholar]
  5. Colquhoun D., Neher E., Reuter H., Stevens C. F. Inward current channels activated by intracellular Ca in cultured cardiac cells. Nature. 1981 Dec 24;294(5843):752–754. doi: 10.1038/294752a0. [DOI] [PubMed] [Google Scholar]
  6. Fedida D., Noble D., Shimoni Y., Spindler A. J. Inward current related to contraction in guinea-pig ventricular myocytes. J Physiol. 1987 Apr;385:565–589. doi: 10.1113/jphysiol.1987.sp016508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hauswirth O. Effects of halothane on single atrial, ventricular, and Purkinje fibers. Circ Res. 1969 May;24(5):745–750. doi: 10.1161/01.res.24.5.745. [DOI] [PubMed] [Google Scholar]
  8. Ikemoto Y., Yatani A., Arimura H., Yoshitake J. Reduction of the slow inward current of isolated rat ventricular cells by thiamylal and halothane. Acta Anaesthesiol Scand. 1985 Aug;29(6):583–586. doi: 10.1111/j.1399-6576.1985.tb02258.x. [DOI] [PubMed] [Google Scholar]
  9. Kimura J., Noma A., Irisawa H. Na-Ca exchange current in mammalian heart cells. Nature. 1986 Feb 13;319(6054):596–597. doi: 10.1038/319596a0. [DOI] [PubMed] [Google Scholar]
  10. Lain R. F., Hess M. L., Gertz E. W., Briggs F. N. Calcium uptake activity of canine myocardial sarcoplasmic reticulum in the presence of anesthetic agents. Circ Res. 1968 Nov;23(5):597–604. doi: 10.1161/01.res.23.5.597. [DOI] [PubMed] [Google Scholar]
  11. Lee K. S., Marban E., Tsien R. W. Inactivation of calcium channels in mammalian heart cells: joint dependence on membrane potential and intracellular calcium. J Physiol. 1985 Jul;364:395–411. doi: 10.1113/jphysiol.1985.sp015752. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lee K. S., Tsien R. W. Mechanism of calcium channel blockade by verapamil, D600, diltiazem and nitrendipine in single dialysed heart cells. Nature. 1983 Apr 28;302(5911):790–794. doi: 10.1038/302790a0. [DOI] [PubMed] [Google Scholar]
  13. Lee K. S., Tsien R. W. Reversal of current through calcium channels in dialysed single heart cells. Nature. 1982 Jun 10;297(5866):498–501. doi: 10.1038/297498a0. [DOI] [PubMed] [Google Scholar]
  14. Lynch C., 3rd, Vogel S., Sperelakis N. Halothane depression of myocardial slow action potentials. Anesthesiology. 1981 Oct;55(4):360–368. doi: 10.1097/00000542-198110000-00005. [DOI] [PubMed] [Google Scholar]
  15. Matsuda H., Noma A. Isolation of calcium current and its sensitivity to monovalent cations in dialysed ventricular cells of guinea-pig. J Physiol. 1984 Dec;357:553–573. doi: 10.1113/jphysiol.1984.sp015517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mechmann S., Pott L. Identification of Na-Ca exchange current in single cardiac myocytes. Nature. 1986 Feb 13;319(6054):597–599. doi: 10.1038/319597a0. [DOI] [PubMed] [Google Scholar]
  17. Merin R. G., Kumazawa T., Honig C. R. Reversible interaction between halothane and Ca++ on cardiac actomyosin adenosine triphosphatase: mechanism and significance. J Pharmacol Exp Ther. 1974 Jul;190(1):1–14. [PubMed] [Google Scholar]
  18. Miller M. S., Gandolfi A. J. A rapid, sensitive method for quantifying enflurane in whole blood. Anesthesiology. 1979 Dec;51(6):542–544. doi: 10.1097/00000542-197912000-00012. [DOI] [PubMed] [Google Scholar]
  19. Mitchell M. R., Powell T., Terrar D. A., Twist V. W. Calcium-activated inward current and contraction in rat and guinea-pig ventricular myocytes. J Physiol. 1987 Oct;391:545–560. doi: 10.1113/jphysiol.1987.sp016755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Mitchell M. R., Powell T., Terrar D. A., Twist V. W. Characteristics of the second inward current in cells isolated from rat ventricular muscle. Proc R Soc Lond B Biol Sci. 1983 Oct 22;219(1217):447–469. doi: 10.1098/rspb.1983.0084. [DOI] [PubMed] [Google Scholar]
  21. Mitchell M. R., Powell T., Terrar D. A., Twist V. W. Influence of a change in stimulation rate on action potentials, currents and contractions in rat ventricular cells. J Physiol. 1985 Jul;364:113–130. doi: 10.1113/jphysiol.1985.sp015734. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mitchell M. R., Powell T., Terrar D. A., Twist V. W. Ryanodine prolongs Ca-currents while suppressing contraction in rat ventricular muscle cells. Br J Pharmacol. 1984 Jan;81(1):13–15. doi: 10.1111/j.1476-5381.1984.tb10735.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mullins L. J. The generation of electric currents in cardiac fibers by Na/Ca exchange. Am J Physiol. 1979 Mar;236(3):C103–C110. doi: 10.1152/ajpcell.1979.236.3.C103. [DOI] [PubMed] [Google Scholar]
  24. Pask H. T., England P. J., Prys-Roberts C. Effects of volatile inhalational anaesthetic agents on isolated bovine cardiac myofibrillar ATPase. J Mol Cell Cardiol. 1981 Mar;13(3):293–301. doi: 10.1016/0022-2828(81)90317-5. [DOI] [PubMed] [Google Scholar]
  25. Powell T., Terrar D. A., Twist V. W. Electrical properties of individual cells isolated from adult rat ventricular myocardium. J Physiol. 1980 May;302:131–153. doi: 10.1113/jphysiol.1980.sp013234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Prys-Roberts C., Gersh B. J., Baker A. B., Reuben S. R. The effects of halothane on the interactions between myocardial contractility, aortic impedance, and left ventricular performance. I. Theoretical considerations and results. Br J Anaesth. 1972 Jul;44(7):634–649. doi: 10.1093/bja/44.7.634. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Sonntag H., Donath U., Hillebrand W., Merin R. G., Radke J. Left ventricular function in conscious man and during halothane anesthesia. Anesthesiology. 1978 May;48(5):320–324. doi: 10.1097/00000542-197805000-00004. [DOI] [PubMed] [Google Scholar]
  29. Su J. Y., Kerrick W. G. Effects of halothane on caffeine-induced tension transients in functionally skinned myocardial fibers. Pflugers Arch. 1979 May 15;380(1):29–34. doi: 10.1007/BF00582608. [DOI] [PubMed] [Google Scholar]
  30. Wilson W. A., Goldner M. M. Voltage clamping with a single microelectrode. J Neurobiol. 1975 Jul;6(4):411–422. doi: 10.1002/neu.480060406. [DOI] [PubMed] [Google Scholar]

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