Issue

Vol. 64 No. 13: Issue 13

The undersigned hereby assign all rights, included but not limited to copyright, for this manuscript to CMB Association upon its submission for consideration to publication on Cellular and Molecular Biology. The rights assigned include, but are not limited to, the sole and exclusive rights to license, sell, subsequently assign, derive, distribute, display and reproduce this manuscript, in whole or in part, in any format, electronic or otherwise, including those in existence at the time this agreement was signed. The authors hereby warrant that they have not granted or assigned, and shall not grant or assign, the aforementioned rights to any other person, firm, organization, or other entity. All rights are automatically restored to authors if this manuscript is not accepted for publication.

The role of PLC-IP3 cascade on 4-aminopyridine (4-AP) contracture in electrically-driven rat atrial and diaphragmatic strips: new evidence by neomycin and heparin

https://doi.org/10.14715/cmb/2018.64.13.6
Ozlem Kucukhuseyin
Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, 34093 Capa, Istanbul, Turkey
Sumbul Khalid
Department of Bioinformatics and Biotechnology, International Islamic University, Islamabad, Pakistan
Uteuliyev Yerzhan Sabitaliyevich
Kazakhstan Medical University KSPH, Almaty, Kazakhstan
Cihat Kucukhuseyin
Department of Medical Pharmacology, Istanbul University Cerrahpasa Medical Faculty, 34098 Cerrahpasa, Istanbul, Turkey

Corresponding Author(s) : Ozlem Kucukhuseyin

ozlemkh@istanbul.edu.tr

Cellular and Molecular Biology, Vol. 64 No. 13: Issue 13

Abstract

Induction of cardiac contractures by 4-AP in Ca2+-free medium implied the involvement of SR and PLC-IP3 cascade. Thus, the role of PLC-IP3 cascade against contractile actions of 4-AP in electrically-driven rat atrial and diaphragmatic strips were studied both in the presence, and absence of Ca2+ using neomycin, a PLC inhibitor, and heparin, an IP3-R antagonist. 4-AP was applied cumulatively in logarithmically increasing concentrations in the range of 1-16µg/ml, and the preparations were treated with neomycin (400µM) or heparin (400µg/ml) for 3min prior to 4-AP injection. Post-rest potentiation in atrial strips was obtained by interruption of stimulation for 30min. 4-AP caused biphasic alteration in twitch amplitudes, as initially increased up to 16mM and then depressed due to contracture development, which were not affected significantly by neomycin and heparin. Both atrial and denervated diaphragmatic strips challenged to 4-AP in the presence and absence of Ca2+ developed dose dependent contractures which were significantly antagonized both by neomycin and heparin (p<0.05). Post-rest first contractions in controls were found to be reduced by 2min exposure to 4mM 4-AP and augmented by 3min exposure to heparin alone. 4-AP responses in the presence of neomycin and heparin were significantly higher than with those only treated with 4-AP alone and lesser than controls. Because of the fact that 4-AP inducing contracture in Ca2+-free medium, Ca2+ causing contracture should be of SR in origin. Depending on these results, it was concluded that activation of PLC-IP3 cascade by 4-AP is involved in the mediation of contracture and contractile actions of this molecule.

Keywords

4-AP Contracture PLC IP3 SR Neomycin Heparin.
Kucukhuseyin, O., Khalid, S., Sabitaliyevich, U. Y., & Kucukhuseyin, C. (2018). The role of PLC-IP3 cascade on 4-aminopyridine (4-AP) contracture in electrically-driven rat atrial and diaphragmatic strips: new evidence by neomycin and heparin. Cellular and Molecular Biology, 64(13), 26–32. https://doi.org/10.14715/cmb/2018.64.13.6
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX
References
  1. Anderson TW, Hirsch C, Kavaler F. Mechanism of activation of contraction in frog ventricular muscle. Circ Res. 1977; 41(4): 472-480.
  2. Beeler GW, Reuter H. Membrane calcium currents in ventricular myocardial fibres. J Physiol 1970; 207(1): 191-209.
  3. Beeler GW, Reuter H. Voltage-clump experiments in ventricular myocardial fibres. J Physiol 1970; 207(1): 165-190.
  4. Bhaskar A, Subbana PK, Arasan S, Rajapathy J, Rao JP, Subramani S. 4-Aminopyridine-induced contracture in frog ventricle is due to calcium released from intracellular stores. Indian J Physiol Pharmacol. 2008; 52(4): 366-374.
  5. Berridge MJ. Inositol triphosphate and calcium signalling. Nature. 1993; 361(6410): 315-325, 1993.
  6. Estrade M, Cardenas C, Liberona JL, Carrasco MA, Mignery GA, Allen PD, Jaimovich E. Calcium transients 1B5 myotubes lacking ryanodine receptors are related to inositol triphosphate receptors. J Biol Chem. 2001; 276(25):22868-22874.
  7. Fabiato A. Calcium-induced release of calcium from the cardiac sarcoplasmic reticulum. Am J Physiol.1983; 245 (1): Cl-14.
  8. Fan JS, Palade P. One calcium ion may suffice to open tetrameric cardiac ryanodine receptor in rat ventricular myocites. J Physiol. 1999; 516: 769-780.
  9. Freeman SE. Cholinergic mechanisms in heart: Interactions with 4-aminopyridine. J Pharmacol Exp Ther. 1979; 210(1): 7-14.
  10. Fukami K, Inanobe S, Kanemaru K, Nakamura Y. Phospholipase C is a key enzyme regulating intracellular calcium and modulating the phosphoinositide balance. Prog Lipid Res. 2010; 49(4): 429-437.
  11. Giannini G, Conti A, Mammarella S, Scrobogna M, Sorrentino V. The ryanodine receptor/calcium channel genes are widely and differentially expressed in murine brain and peripheral tissues. J Cell Biol. 1995; 128(5): 893-904.
  12. Iino M, Kobayashi T, Endo M. Use of ryanodine for functional removal of calcium store in smooth muscle cells of the guinea pig. Biochem Biophys Res Commun. 1988; 152(1): 417-422.
  13. Iino M. Calcium dependent inositol triphosphate-induced calcium release in guinea pig taenia caeci. Biochem Biophys Res Commun. 1987; 142(1): 47-52.
  14. Ishida Y, Honda H. Inhibitory action of 4-aminopyridine on Ca(2+)-ATPase of the mammalian sarcoplasmic reticulum. J Biol Chem. 1993; 268(6): 4021-4024.
  15. Jaimovich E, Rojas E. Intracellular Ca2+ transients induced by high external K+ and tetracain in cultered rat myotubes. Cell Calcium. 1994; 15(5): 356-368.
  16. Jeanne AP, Maria AC, Dany SA, Beatrice D, Juan R, Marioly M, Manuel E, Enrique J. IP3 receptor function and localization in myotubes: an unexplored Ca2+ signaling pathway in skeletal muscle. J Cell Science 2001; 114: 3673-3683.
  17. Jeck C, Pinto J, Boyden P. Transient outward currents in subendocardial Purkinje myocytes surviving in the infarcted heart. Circulation 1995, 92(3): 465-473.
  18. Keizer J, Levine L. Ryanodine receptor adaptation and Ca2+(-)induced Ca2+ release-dependent Ca2+ oscillations. Biophys J. 1996; 71(6): 3477–3487.
  19. Kucukhuseyin C, Lullman H. Inhibition of 45 Ca2+ - binding to phosphatidylserine monolayer by 4-aminopyridine. Med Bull 1st Med Fac. 1986; 19: 75
  20. Kucukhuseyin C. Effects of 4-aminpyridine on calcium exchange in guinea-pig papillary muscle. J Clin Exp Pharmacol Ther. 1990; 3: 39-44.
  21. Kucukhuseyin C, Silan C. Induction of calcium-dependent action potentials by 4-aminopyridine in potassium depolarized guinea-pig papillary muscle. J Basic Clin Physiol Pharmacol. 1997; 8(1-2): 81-89.
  22. Kucukhuseyin C, Oncel H, Silan C. On the mechanism of post-rest adaptation in the isolated electrically drivenleft atria of rats. J Basic Clin Physiol Pharmacol. 2002; 13(4): 263-288.
  23. Liu QY, Rasmusson RL, Liu QX, Strauss HC. Voltage-dependent, open channel blockade of the cardiac sarcoplasmic reticulum potassium channel by 4-aminopyridine. Can J Cardiol. 1998, 14(2): 275-280.
  24. Llinas R, Walton K, Bohr V. Synaptic transmission in squid giant synapse after potassium conductance blockade with external 3- and 4-aminopyridine Biophys J. 1976; 16(1): 83-86.
  25. Ma L, Michel WC. Drugs Affecting Phospholipase C-Mediated Signal Transduction Block the Olfactory Cyclic Nucleotide-Gated Current of Adult Zebrafish. J Neurophysiol. 1998, 79(3): 1183-1192.
  26. Mhaouty-Kodja S, Houdeau E, Legrand C. Regulation of myometrial phospholipase C system and uterine contraction by beta-adrenergic receptors in midpregnant rat. Biol Reprod. 2004; 70(3): 570-576.
  27. Otsu K, Willard HF, Khanna VK, Zorzato F, Green NM, MacLennan DH. Molecular cloning of cDNA encoding the Ca2+ release channel (ryanodine receptor) of rabbit cardiac muscle sarcoplasmic reticulum. J Biol Chem 1990; 265(23): 13472-13483.
  28. Ozgul M, Silan C, Yillar O, Kucukhuseyin C. 4-Aminopyridine can induce release of calcium from the sarcoplasmic reticulum of frog heart. J Basic Clin Physiol Pharmacol. 2000;11(1):57-62.
  29. Palnitkar SS, Bin B, Jimenez LS, Morimoto H, Williams PG, Paul-Pletzer K, Parness J. [3H]Azidodantrolene: synthesis and use in identification of a putative skeletal muscle dantrolene binding site in sarcoplasmic reticulum. J Med Chem. 1999; 42(11): 1872-1880.
  30. Paul-Pletzer K, Palnitkar SS, Jimenez LS, Morimoto H, Parness J. The skeletal muscle ryanodine receptor identified as a molecular target of [3H]azidodantrolene by photoaffinity labeling. Biochemistry. 2001; 40(2): 531-542.
  31. Pelhate M, Pichon Y. Proceedings: Selective inhibition of potassium current in the giant axon of the cockroach. J Physiol. 1974; 242(2): 90P-91P.
  32. Rasmusson RL, Zhang Y, Campbell DL, Comer MB, Castellino RC, Liu S, Strauss HC. Bi-stable block by 4-aminopyridine of a transient K+ - channel (Kv1.4) cloned from ferret ventricle and expressed in Xenopus oocytes. J Physiol. 1995; 485(Pt 1): 59-71.
  33. Schoepke HG, Shideman FE. The cardiac effects of certain pyridine derivatives and their corresponding N-oxides. J Pharmacol Exp Ther 1962; 135: 358-566.
  34. Sutko JL, Airey JA. Ryanodine receptor Ca2+ release channels: Does diversity in form equal diversity in function?. Physiol Rev. 1996; 76(4): 1027-1071.
  35. Thompson M, Kliewer A, Maass D, Becker L, White DJ, Bryant D, Arteaga G, Horton J, Giroir BP. Increased cardiomyocyte intracellular calcium during endotoxin-induced cardiac dysfunction in guinea pigs. Pediatric Research. 2000; 47(5): 669-676.
  36. Zavecz JH. Theophylline affects the inotropic status of guinea-pig lefty atria by actions on the sarcolemma and sarcoplasmic reticulum. Eur J Pharmacol. 1989; 160(1): 187-191.
  37. Zhao M, Li P, Li X, Zhang L, Winkfein RJ, Chen SR. Molecular identification of the ryanodine receptor pore-forming segment. J Biol Chem 1999; 274(37): 25971-25974.
Read More
Author biographies is not available.
Crossref
Scopus
Google Scholar
Europe PMC
Download this PDF file
PDF
Statistic
Read Counter : 954 Download : 374

Most read articles by the same author(s)

<< < 1 2 3 > >> 

Similar Articles

You may also start an advanced similarity search for this article.