The role of potassium channels and calcium in the relaxation mechanism of magnesium sulfate on the isolated rat uterus

Authors

  • Dragana Sokolović Department of Pharmacology, Faculty of Medicine at Foča, University of East Sarajevo, East Sarajevo, 73301 Foča, Republic of Srpska
  • Dragana Drakul Department of Pharmacology, Faculty of Medicine at Foča, University of East Sarajevo, East Sarajevo, 73301 Foča, Republic of Srpska
  • Zorana Oreščanin-Dušić Department for Physiology, Institute for Biological Research ‘‘Siniša Stanković’’, University of Belgrade, 11000 Belgrade http://orcid.org/0000-0002-2772-0134
  • Nikola Tatalović Department for Physiology, Institute for Biological Research ‘‘Siniša Stanković’’, University of Belgrade, 11000 Belgrade http://orcid.org/0000-0002-0745-8845
  • Milica Pecelj 1. Faculty of Philosophy, University of East Sarajevo, Pale, Republic of Srpska, Bosnia and Herzegovina; 2. Geographical Institute “Jovan Cvijić” of the Serbian Academy of Sciences and Arts, 11000 Belgrade, Serbia; 3. Institute of Sports, Tourism and Service, South Ural State University, Chelyabinsk, Russia
  • Slobodan Milovanović Department of Pharmacology, Faculty of Medicine at Foča, University of East Sarajevo, East Sarajevo, 73301 Foča, Republic of Srpska http://orcid.org/0000-0003-3164-5242
  • Duško Blagojević Department for Physiology, Institute for Biological Research ‘‘Siniša Stanković’’, University of Belgrade, 11000 Belgrade http://orcid.org/0000-0001-6338-2833

Keywords:

MgSO4, uterus, K channels, Ca2 channels, tocolytic

Abstract

MgSO4 is used as a tocolytic agent. It is considered to be a calcium channel antagonist, but a different mechanism of its action might be involved. The aim of this study was to examine the contribution of calcium concentrations and potassium channels in the mechanism of MgSO4-mediated uterine relaxation. Isolated uteri from female Wister rats were treated with increasing MgSO4 concentrations (0.1-30 mM). MgSO4 induced dose-dependent inhibition of spontaneous activity. Addition of Ca2+ (6 mM and 12 mM) stimulated uterine contractile activity and attenuated the inhibitory activity of MgSO4. In order to analyze the role of different subtypes of potassium channels, Ca2+-stimulated uteri were pretreated with glibenclamide (Glib), a selective ATP-sensitive potassium channel inhibitor (KATP), tetraethylammonium (TEA), a non-specific inhibitor of large conductance calcium-activated potassium channels (BKCa), and 4-aminopyridine (4-AP), a voltage-sensitive potassium channel inhibitor (Kv), at concentrations that had no effect per se. Pretreatment with 4-AP had no effect on MgSO4-mediated relaxation of Ca2+-stimulated uteri. The relaxing effect of MgSO4 was potentiated by pretreatment with glibenclamide. Pretreatment with TEA attenuated the MgSO4-mediated decrease in frequency. Our results suggest that MgSO4 acts as a general calcium antagonist that influences Ca2+-mediated potassium channels. Furthermore, it seems that MgSO4 uterine relaxation activity is partially mediated by selective ATP-sensitive potassium channels, suggesting an ATP-dependent role.

https://doi.org/10.2298/ABS180615031S

Received: June 15, 2018; Revised: July 6, 2018; Accepted: July 6, 2018; Published online: July 16, 2018

How to cite this article: Sokolović D, Drakul D, Oreščanin-Dušić Z, Tatalović N, Pecelj M, Milovanović S, Blagojević D. The role of potassium channels and calcium in the relaxation mechanism of magnesium sulfate on the isolated rat uterus. Arch Biol Sci. 2019;71(1):5-11.

Downloads

Download data is not yet available.

Author Biographies

Dragana Sokolović, Department of Pharmacology, Faculty of Medicine at Foča, University of East Sarajevo, East Sarajevo, 73301 Foča, Republic of Srpska


Dragana Drakul, Department of Pharmacology, Faculty of Medicine at Foča, University of East Sarajevo, East Sarajevo, 73301 Foča, Republic of Srpska


Slobodan Milovanović, Department of Pharmacology, Faculty of Medicine at Foča, University of East Sarajevo, East Sarajevo, 73301 Foča, Republic of Srpska


References

Elliott JP. Magnesium sulfate as a tocolytic agent. Am J Obstet Gynecol. 1983;147(3):277-84.

Gáspár R, Hajagos-Tóth J. Calcium Channel Blockers as Tocolytics: Principles of Their Actions, Adverse Effects and Therapeutic Combinations. Pharmaceuticals. 2013;6:689-99.

Chesley LC. History and epidemiology of preeclampsia-eclampsia. Clinical Obstetrics and Gynecology. 1984;27(4):801-20.

Dorsett L. The intramuscular injection of magnesium sulphate for the control of convulsions in eclampsia. Am J ObstetGynecol. 1926;11:227-31.

Lazard EM. An analysis of 575 cases of eclamptic and pre eclamptic toxaemias treated by IV injections of magnesium sulphate. Am J Obstet Gynecol. 1933;26:647-56.

Hall DG, McGaughey HS, Corey EL, Thornton WN. The effects of magnesium therapy on the duration of labour. Am J Obstet Gynecol. 1959;78:27.

Stallworth JC, Yeh S, Petrie RH. The effect of magnesium sulphate on fetal heart rate variability and uterine activity. Am J ObstetGynecol 1981;140:702-6.

Crowther CA, Hiller JE, Doyle LW. Magnesium sulphate for preventing preterm birth in threatened preterm labour. Cochrane Database Syst Rev. 2002;4:CD001060.

Coleman FH. Safety and efficacy of combined ritodrine and magnesium sulfate for preterm labor: a method for reduction of complications. Am J Perinatol. 1990;7(4):366-9.

Kosasa TS, Busse R, Wahl N, Hirata G, Nakayama RT, Hale RW. Long-term tocolysis with combined intravenous terbutaline and magnesium sulfate: a 10-year study of 1000 patients. Obstet Gynecol. 1994;84(3):369-73.

Hatjis CG, Nelson LH, Meis PJ, Swain M. Addition of magnesium sulfate improves effectiveness of ritodrine in preventing premature delivery. Am J Obstet Gynecol. 1984;150(2):142-50.

Ferguson JE, Hensleigh PA, Kredenster D. Adjunctive use of magnesium sulfate with ritodrine for preterm labor tocolysis. Am J Obstet Gynecol. 1984;148(2):166-71.

Kalezić I, Rodić V, Kitanović S, Milovanović G, Zgradić I, Milovanović S. The effects of ritodrine, on receptors in smooth uterine muscle and heart atria of rats. Arch Toxicol Kinet Xenobiot Metab. 1993;1:112-8.

van Vliet E, Dijkema GH, Schuit E, Heida KY, Roos C, van der Post J, Parry EC, McCowan L, Lyell DJ, El-Sayed YY, Carr DB, Clark AL, Mahdy ZA, Uma M, Sayin NC, Varol GF, Mol BW, Oudijk MA. Nifedipine maintenance tocolysis and perinatal outcome: an individual participant data meta-analysis. BJOG. 2016;123(11):1753-60.

Novaković R, Milovanović SR, Heinle H, Protić D, Gojković-Bukarica Lj. The effect of potassium channel opener pinacidil on non-pregnant rat uterus. Basic Clin Pharmacol Toxicol. 2007;1742-84.

Oreščanin-Dušić Z, Milovanović S, Blagojevic D, Nikolic-Kokić A, Radojičić R, Spasojević I, Spasić BM. Diethyldithiocarbamate potentiates the effects of protamine sulfate in the isolated rat uterus. Redox Rep. 2009;14:48-54.

Oreščanin-Dušić Z, Milovanović S, Radojičić R, Nikolić-Kokić A, Appiah I, Slavić M, Čutura N, Trbojević S, Spasić M, Blagojević D. Effects of protamine sulfate on spontaneous and Ca-induced contractile activity in the rat uterus are potassium channels mediated. Gen. Physiol. Biophys. 2009;28:143-8.

Milovanovic S, Kordic-Bojinović J, Djordjevic S, Drakul D, Sokolovic D, Miletic N, Blagojevic D. The importance of potassium chanels in the relaxing effect of pentoxifillyne on the isolated rat uterus. Serb J Exp Clin Res. 2013;14(2):55-64.

Kuang Q, Purhonen P, Hebert H. Structure of potassium channels. Cell Mol Life Sci. 2015;72:3677-93.

Khan RN, Matharoo BВ, Arulkumaran S, Ashford МL. Potassum channels in the human myometrium. Exp Physiol. 2001;862:255-64.

Morrison ЈЈ, Ashford МLЈ, Khan RN, Smith S K. The effects of potassium channel openers on isolated pregnant human myometrium before and after the onset of labor: potential for tocolysis. Аm Ј Obstet Gynecol. 1993;169:1277-85.

Appiah I, Nikolic-Kokic A, Orescanin-Dusic Z, Radojicic R, Milovanovic S, Spasic M, Blagojevic D. Reversible Oxidation of Myometrial Voltage-Gated Potassium Channels with Hydrogen Peroxide. Oxid Med Cell Longev. 2012;2012:105820.

Kordić-Bojinović J, Oreščanin-Dušić Z, Slavić M, Radojičić R, Spasić M, Milovanović SR, Blagojević D. Effect of indometacin pretreatment on protamine sulfate-mediated relaxation of the isolated rat uterus: the role of the antioxidative defense system. Pharmacol Rep. 2011;63(4):1019-28.

Kordić-Bojinović J, Jokanović D, Stanković D, Janković S, Milovanović S. Influence of modulators of relaxant effect of pentoxifylline in isolated rat uterus. Ser J Exp Clin Res. 2010;11(3):99-104.

Furchgott RF. Pharmacological characterization of receptors: its relation to radioligand-binding studies. Fed Proc. 1978;37(2):115-20.

Marcondes FK, Bianchi FI, Tanno AP. Determination of the estrous cycle phases of rats: some helpful considerations. Braz J Biol. 2002;62:609-14.

Hinkle ED, Wiersma W, Jurs GS. Applied statistics for behavioral sciences. 2nd ed. Boston: Houghton Mifflin Company; 1994.

Manley BFJ. Multivariate statistical methods. 2nd ed. London: Chapman & Hall; 1986.

Romani AMP. Cellular magnesium homeostasis. Arch Biochem Biophys. 2011;512(1):1-23.

Guyton ST, Morey TE. Magnesium. In: Atlee JL, editor. Complications in anesthesia. Philadelphia: Saunders, Elsevier; 2007. p. 59-61.

Zahradnikova A, Palade P. Procaine effects on single sarcoplasmic reticulum Ca2+ release channels. Biophys J. 1993;64:991-1003.

Györke I, Györke S. Regulation of the cardiac ryanodine receptor channel by luminal Ca2+ involves luminal Ca2+ sensing sites. Biophys J. 1998;75:2801-2810.

Laver DR, Baynes TM, Dulhunty AF. Magnesium inhibition of ryanodine-receptor calcium channels: evidence for two independent mechanisms. J Membr Biol. 1997;156:213-229.

Zahradníková A, Dura M. Györke I, Escobar A.L, Zahradník I, Györke S. Regulation of dynamic behavior of cardiac ryanodine receptor by Mg2+ under simulated physiological conditions. Am J Physiol Cell Physiol 2003;285:C1059-70.

Coronado R, Morrissette J, Sukhareva M, Vaughan DM. Structure and function of ryanodine receptors. Am J Physiol Cell Physiol. 1994;266:C1485-504.

Guo F, Zhou PD, Gao QH, Gong J, Feng R, Xu XX, Liu SY, Hu HY, Zhao MM, Adam HC, Cai JQ, Hao LY. Low-Mg2+ treatment increases sensitivity of voltage-gated Na+ channels to Ca2+/calmodulin-mediated modulation in cultured hippocampal neurons. Am J Physiol Cell Physiol. 2015;308:C594-605.

McCallum LA, Greenwood IA, Tribe RM. Expression and function of Kv7 channels in murine myometrium throughout oestrous cycle. Pflugers Arch. 2009;457:1111-20.

Shi J, Cui J. Intracellular Mg2+ enhances the function of BK-type Ca2+-activated K+ channels. J Gen Physiol. 2001;118:589-605.

Yazejian B, DiGregorio DA, Vergara JL, Poage RE, Meriney SD, Grinnell AD. Direct measurements of presynaptic calcium and calcium-activated potassium currents regulating neurotransmitter release at cultured Xenopus nerve-muscle synapses. J Neurosci. 1997;17(9):2990-3001.

Yazejian B, Sun XP, Grinnell AD. Tracking presynaptic Ca2+ dynamics during neurotransmitter release with Ca2+-activated K+ channels. Nat Neurosci. 2000;3(6):566-71.

Marrion NV, Tavalin SJ. Selective activation of Ca2+-activated K+ channels by co-localized Ca2+ channels in hippocampal neurons. Nature. 1998;29:900-5.

Jaggar JH, Porter VA, Lederer WJ, Nelson MT. Calcium sparks in smooth muscle. Am J Physiol Cell Physiol. 2000;278(2):C235-56.

Neher E. Usefulness and limitations of linear approximations to the understanding of Ca++ signals. Cell Calcium. 1998;24(5-6):345-57.

Suh BC, Hille B. Electrostatic interaction of internal Mg2+ with membrane PIP2 Seen with KCNQ K+ channels. J Gen Physiol. 2007;130(3):241-56.

Scarpa A, Brinley FJ. In situ measurements of free cytosolic magnesium ions. Fed Proc. 1981;40(12):2646-52.

Lüthi D, Günzel D, McGuigan JA. Mg-ATP binding: its modification by spermine, the relevance to cytosolic Mg2+ buffering, changes in the intracellular ionized Mg2+ concentration and the estimation of Mg2+ by 31P-NMR. Exp Physiol. 1999;84(2):231-52.

Downloads

Published

2019-04-02

How to Cite

1.
Sokolović D, Drakul D, Oreščanin-Dušić Z, Tatalović N, Pecelj M, Milovanović S, Blagojević D. The role of potassium channels and calcium in the relaxation mechanism of magnesium sulfate on the isolated rat uterus. Arch Biol Sci [Internet]. 2019Apr.2 [cited 2024Dec.22];71(1):5-11. Available from: https://serbiosoc.org.rs/arch/index.php/abs/article/view/3064

Issue

Section

Articles

Most read articles by the same author(s)