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Effects of Sodium and Calcium Channel Blockade on Cytosolic Calcium Oscillations and Phasic Contractions of Myometrial Tissue

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Abstract

Objective

These studies sought to test the hypothesis that agonist-stimulated cytosolic calcium oscillations and phasic myometrial contractions are dependent on calcium influx through dihydropyridine-sensitive calcium channels, but not sodium influx through teirodotoxin-sensitive sodium channels.

Methods

Cytosolic calcium imaging studies and in vitro isometric contraction studies were performed using uterine tissue from proestrus/estrus Sprague-Dawley rats. The calcium imaging studies were performed after loading partial thickness strips of myometrium with Fura-2. For the in vitro isometric contraction studies, the contraction data were computer digitalized, analyzed for contraction area, and normalized for cross-section area. Tire effects of nifedipine (1.0–5 μmol/L), a calcium channel blocker, were compared to tetrodotoxin (0.01–1 μmol/L), a sodium channel blocker.

Results

Oxytocin-stimulated simultaneous cytosolic calcium oscillations and phasic contractions were completely inhibited by 1 μmol/L nifedipine; in contrast, 1 μmol/L tetrodotoxin had no effect on the oxytocin-stimulated calcium oscillations and contractions. Oxytocin, aluminum fluoride, potassium chloride, and ionomycin stimulated in vitro phasic myometrial contractions. Tetrodotoxin had no effect on these agonist-stimulated phasic contractions, whereas nifedipine produced a significant, dose-related inhibition of the phasic contractile activity.

Conclusions

The studies described in this report support the hypothesis that the influx of extracellular calcium is an important component of the cellular mechanisms responsible for the cytosolic calcium oscillations occurring during phasic myometrial contractions. In contrast, sodium influx through tetrodotoxin-sensitive sodium channels does not appear to play a comparably important role.

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References

  1. Kuriyama H, Suzuki H. Changes in electrical properties during gestation and following hormonal treatments. J Physiol 1976;260: 315–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Inoue Y, Nakao K, Okabe K, Izumi H, Kanda S, Kitamura K, Kuriyama H. Some electrical properties of human pregnant myometrium. Am J Obstet Gynecol 1990;162:1090–8.

    Article  CAS  PubMed  Google Scholar 

  3. Catterall WA. Structure and function of voltage-sensitive ion channels. Science 1988;242:50–61.

    Article  CAS  PubMed  Google Scholar 

  4. Katz AM. Cardiac ion channels. New Ing J Med 1993;328: 1244–51.

    Article  CAS  Google Scholar 

  5. Young RC, Herdon-Smith L. Characterization of sodium channels in cultured human uterine smooth muscle cells. Am J Obstet Gynecol 1991;164:175–81.

    Article  CAS  PubMed  Google Scholar 

  6. Sperelakis N, Inoue Y, Ohya Y. Fast Na+ channels and slow Ca2+ current in smooth muscle from pregnant rat uterus. Mol Cell Biochem 1992;114:79–89.

    Article  CAS  PubMed  Google Scholar 

  7. Poli E, Merialdi A, Coruzzi G. Characterization of the spontaneous motor activity of the isolated human pregnant myometrium. Pharm Research 1990;22:115–24.

    Article  CAS  Google Scholar 

  8. Holmes-Childress C, Katz VL. Nifedipine and its indications in obstetrics and gynecology. Obstet Gynecol 1994;83:616–24.

    Article  Google Scholar 

  9. Phillippe M. Mechanisms underlying phasic contractions of pregnant rat myometrium stimulated with aluminum fluoride. Am J Obstet Gynecol 1994:170:981–90.

    Article  CAS  PubMed  Google Scholar 

  10. Phillippe M, Chien E, Freij M, Saunders T. Ionomycin-stimulated phasic myometrial contractions. Am J Physiol 1995;269:E779–85.

    Google Scholar 

  11. Chien EK, Saunders T, Phillippe M. The mechanisms underlying Bay K 8644-stimulated phasic myometrial contractions. J Soc Gynecol Invest 1996;3:106–12.

    Article  CAS  Google Scholar 

  12. Phillippe M, Chien EK. Potassium chloride effects on the hormonal signal transduction mechanisms underlying phasic myometrial contractions. J Endocrinol 1995;146:485–93.

    Article  CAS  PubMed  Google Scholar 

  13. Tasaka K, Masumoto N, Miyake A, Tanizawa O. Direct measurement of intracellular free calcium in cultured human puerperal myometrial cells stimulated by oxytocin: Effects of extracellular calcium and calcium channel blockers. Obstet Gynecol 1991;77:101–6.

    CAS  PubMed  Google Scholar 

  14. Campbell D. Large and small vertebrate sensory neurons express different Na and K channel subtypes. Proc Natl Acad Sci 1992:89:9569–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Sculptoreanu A, Morton M, Gartside CL, Hauschka SI, Catterall WA, Scheuer T. Tetrodotoxm-insensitive sodium channels in a cardiac cell line from a transgenic mouse. Am J Physiol 1992; 262:C724–30.

    Article  Google Scholar 

  16. Anwer K, Sanborn BM. Changes in intracellular free calcium in isolated myometrial cells: Role of extracellular and intracellular calcium and possible involvement of guanine nucleotide-sensitive proteins. Endocrinol 1989;124:17–23.

    Article  CAS  Google Scholar 

  17. Anwer K, Hovington JA, Sanborn BM. Involvement of protein kinase A in the regulation of intracellular free calcium and phos-phoinositide turnover in rat myometrium. Biol Reprod 1990;43: 851–9.

    Article  CAS  PubMed  Google Scholar 

  18. Phaneuf S, Europe-Finner GN, MacKenzie IZ, Watson SP, Lopez Barnal A. Oxytocin-stimulated phosphoinositide hydrolysis in human myometrial cells: Involvement of pertussis toxin-sensitive and -insensitive G-proteins. J Endocrinol 1993;136: 497–509.

    Article  CAS  PubMed  Google Scholar 

  19. Yu CY, Qian A, Wen Y, Anwer K, Sanborn BM. Oxytocin stimulates myometrial guanosine trisphosphatase and phospholi-pase-C activities via coupling to Gaq/11. Endocrinol 1995;136: 1509–15.

    Article  Google Scholar 

  20. Szal SE, Repke JT, Seeley EW, Graves SW, Parker CA, Morgan KG. [Ca2+ signaling in pregnant human myometrium. Am J Physiol 1994;267:E77–E87.

    CAS  PubMed  Google Scholar 

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This research was funded by the National Institute of Child Health and Human Development (HD22063, HD28506).

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Phillippe, M., Basa, A. Effects of Sodium and Calcium Channel Blockade on Cytosolic Calcium Oscillations and Phasic Contractions of Myometrial Tissue. Reprod. Sci. 4, 72–77 (1997). https://doi.org/10.1016/S1071-5576(97)00015-4

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  • DOI: https://doi.org/10.1016/S1071-5576(97)00015-4

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