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Vol. 64 No. 13: Issue 13

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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
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