Українська English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2001; 47(2): 24-31


The effects of sex hormones on herg-potassiumchannels expressed in xenopus oocytes

V. M. Osipenko, V. E. Degtiar, V. G. Naidionov, Y. M. Shuba

    A. A. Bogomoletz Institute of PhysiologyNational Academy of Sciences of Ukraine;International Center of Molecular PhysiologyNational Academy of Sciences of Ukraine, Kiev



Abstract

The repolarisation phase of cardiac action potential is characterized by sexual dimorphism suggesting the role of sex steroid hormones in the regulation of K+ channels. Here we report on the effects of testosterone and 17?-estradiol on HERG-encoded K+ channels, expressed in Xenopus oocytes. At 1M concentration testosterone decreased the amplitude of HERG-directed IKr (rapid component of cardiac delayed rectifier K+ current) by 30 % within 30 min of exposure, while 17-estradiol had no effect. Testosterone did not alter the HERG channels kinetics, voltage-dependance, steady- state activation and inactivation properties suggesting that its action most probably involves the decrease of channels open probability and/or the level of their expression. The signaling pathways mediating testosterone-induced down-regulation of HERG channels in Xenopus oocytes remains to be elucidated. The effect of testosterone on HERG channels in Xenopus oocytes is opposite to what one might expect from shorter cardiac action potential duration and electrocardiographic QT-interval in males compared to females.

References

  1. СПИСОК ЛІТЕРАТУРИ
  2. Abbott G.W., Szti F., Splawski I. et. al. MiRP1 forms Ikr potassium channel with HERG and is associated with cardiac arrhythmia // Cell. — 1999. — 97. — P. 175-187.
  3. Barhanin J., Lesage F., Guillemare E. et. al KvLQT1 and Isk (minK) proteins associate to form Iks cardiac potassium current // Nature. — 1996. — 384. — P. 78-80.
  4. Blumental E.M., Kaczmarek L.K. Modulation by cAMP of a slowly activating potassium channel expressed in Xenopus oocytes // J. Neurosci. — 1992. — 12. — P. 290-296.
  5. Bruggeman A., Stuhmer W., Pazdol A. et. al. Mitosis-promoting factor-mediated suppression of a cloned delayed rectifier potassium channel expressed in Xenopus oocytes // Proc. Natl. Acad. Sci.USA. — 1997. — 94. — P. 537-542.
  6. Deal K. K., England S. K., Tamkun M. M. Molecular Physiology of Cardiac Potassium Channels // Physiol. Rev. — 1996. — 76. — № 1. — P. 49-67.
  7. Drici M.D., Burklow T., Haridasse V. et. al. Sex hormons prolong the QT-interval and downregulate potassium channel expression in the rabbit heart // Circulation. — 1996. — 94, 6, Sep. — P.1471-1474.
  8. Erulkar S.D. The influence of 17-beta-oestradiol on K+ currents in smooth muscle cells isolated from immature rat uterus // Proc. R. Soc. Lond. — 1994. — 256. — P. 59-65.
  9. Folander K., Smith J.S., Antanavage J. et. al. Cloning and expression of the delayed- rectifier Isk channel from neonatal rat heart and diethylstilbestrolprimed rat uterus / / Proc. Natl. Acad. Sci.USA. — 1990. — 87. — P. 2975-2979.
  10. 9. Felipe A., Knittle T.J., Doyle K.L. et. al. Differential expression of Isk mRNAs in mouse tissue during development and pregnancy // Amer. J. Physiol. — 1994. — 267. — P. C700-C705. Вплив статевих гормонів
  11. 2 № ,74 .Т ,1002 ,.нруж .лоізіФ 9848-1020 NSSI31
  12. 10. Fortune J.E. Steroid production by Xenopus ovarian follicles at different developmental stages // Dev. Biol. — 1983. — 99. — P. 502-509.
  13. Fortune J.E., Tsang P.C. Production of androgen and estradiol-17b by Xenopus ovaries treated with gonadotropin in vitro // Gen. Comp. Endocrinol. — 1981. — 43. — P. 234-242.
  14. Goldin A.L. Maintenance of Xenopus Laevis and Oocyte Injection // Methods in Enzymology. — 1992. — 207, chapter 15. — P. 266-279.
  15. Janse M.J., Wilde A.A. Molecular mechanisms of arrhytmias // Rev. Port. Cardiol. — 1998. — 2. — P. 1141-1146.
  16. Joels M., Karst H. Effects of estradiol and progesteron on voltage-gated calcium and potassium conductances in rat CA1 hippocampal neurons // J. Neurosci. — 1995. —
  17. 15. — P. 4289-4297.
  18. Kado R.T., Marcher K., Ozon R. et al. Electrical membraine properties of the Xenopus laevis oocyte during progesteron-induced meiotic maturation // Dev. Biol. — 1981.— 84. — P. 471-476.
  19. Kawasaki R. Increased propencity of woman to develop torsades de pointes during complete heart block // J. Cardiovasc. Electrophysiol. — 1995. — 6. — P. 1032-1038.
  20. Le Goascogne C., Sananes N., Gouezou M. et. al. Testosteron-іnduced meiotic maturation of Xenopus laevis ocytes: evidance for an early in the synergetic action of insulin // Developmental Biology. — 1985. — 109. — P. 9-14.
  21. Lin A. L. Sexual dimorphism characterizes baboon myocardial androgen receptors but not myocardial estrogen and progesteron receptors // J. Steroid Biochem. Mol. Biol.— 1990. — 37. — P. 85-95.
  22. 19. Makkar R.R., From B.S., Steinmann R.T. et. al. Female gender as a risk factor for Torsades de Pointes associated with cardiovascular drugs // JAMA. — 1993. — 270. — P. 2590-2597.
  23. 20. McDonald T.V., Yu Z., Ming Z. et. al. A minK-HERG complex regulates the cardiac potassium current Ikr // Nature. — 1997. — 388. — P. 289-292.
  24. McEwen B.S. Non-genomic and genomic effects of steroids on neural activity // TiPS. — 1991. — 12. — P. 141-147.
  25. Mendoza C., Soler A., Tesarik J. et. al. Nongenomic steroid action independent targetting of a plasma membraine calcium channel and a tyrozine kinase // Biochem. Biophys. Res. Com. — 1995. — 210. — P. 518-523.
  26. Rautaharju P.M., Zhou S.H., Wong S. et.al. Sex differences in the evolution of the electrocardiographic QT-interval with age //Can. J. Cardiol.— 1992.— 8.— P.690-695.
  27. Sanguinetti M.C., Jiang C., Curran M.E. et.al. A mechanistic Link Between an Inherited and an Acquired Cardiac Arrhytmia: HERG Encodes the Ikr Potassium Channel // Cell. — 1995. — 81. — P. 299-307.
  28. Sanguinetti M.C., Curran M.E., Zou A. et. al. Coassembly of KvLQT1 and minK(Isk) proteins to form cardiac Iks potassium channel // Nature. — 1996. — 384. — P. 80- 83.
  29. Smith D. The induction of oocyte maturation: transmembraine signalling events and regulation of the cell cycle // Development. — 1989. — 107. — P. 685-699.
  30. Viskin S. Long QT syndromes and torsade de pointes // Lancet. — 1999. — 354, Nov. — P. 1625-33.
  31. Waldegger S., Lang U., Herzer T. et. al. Inhibition of minK protein induced K+ channels in Xenopus oocytes by estrogenes // Naunyn-Schmied Arch. Pharmacol.— 1996. — 354. — P. 698-702.
  32. 29. Zareba W., Locati E.H., Moss A. J. et. al. Age- and sex-related differences in clinical manifestations in patients with congenital long-QT // Circulation. — 1998. — 97, N22, Jun. — P. 2237-2244.

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2024.