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 УЧРЕДИТЕЛИ:
Федеральное государственное бюджетное учреждение науки
"Институт токсикологии Федерального медико-биологического агентства"
(ФГБУН ИТ ФМБА России)

Институт теоретической и экспериментальной биофизики Российской академии наук.

ООО "ИЦ КОМКОН".




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199406, Санкт-Петербург, ул.Гаванская, д. 49, корп.2

ISSN 1999-6314

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«
Vol. 16, Art. 104 (pp. 1184-1194)    |    2015       
»

Impact of some cationic channels blockers on the activation of rat papillary muscles and aorta rings by ammonium ions.
Averin A.S.1, Nakipova O.V.1, Andreeva L.A.1, Averina I.V.1, Sergeev А.I.1, Grishina E.V.2, Galimova M.H.2, Nenov N.M., Dynnik V.V.2

1Federal State Budget Organization of Science ,Institute of Cell Biophysics RAS, 142290, Pushchino, Russia, Institutskaya 3
2Federal State Budget Organization of Science, Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, 142290, Pushchino, Russia, Institutskaya 3



Brief summary

Abstract Main purpose of this work is to investigate the effects of coenzyme NAD+ and of some cationic channels or receptors blockers on the activation of rat myocardial papillary muscle strips (PMS) and aorta rings (AR) by ammonium ions. Isometric contractions force F1 of electrically stimulated PMS (0,03 to 0,3Hz ) and the force F2 of periodic contractions of AR, precontracted by phenylephrine (PE) or serotonin (5-HT), were recorded. It was shown that NH4Cl (1-5 mM) may result in the increase of force F1 of PMS and of force F2 of AR, both by 20-30%. In the presence of NAD+ (1−3 mM), registered values of F1 and F2 were reduced by 50-60%. The effect of NAD+ was completely eliminated, after preincubation of PMS with P2- purinoreceptors blockers (Reactive Blue). In AR the recovery of F2 in the presence of Reactive Blue was not complete (40−50% of control F0). Application of NH4Cl (3−5mM) to PMS, pretreated with NAD+, eliminated hyperpolarizing effect of NAD+ , by causing an increase of force F1 to 120−130% of control force F0. In AR, the additions of NH4Cl (1−10 mM) were characterized by biphasic dose-dependent effects, in which initial decline in force F2 were substituted by the overshoots with final plateau phase F2 values lower than F0. NH4Cl (1-5 mM) suppresses Ca++ -currents of potential- dependent Ca++ L-type channels in isolated cardiomyocytes. Observed effects of NH4Cl on PMS disappear in the presence of ZD 7288 (20−30 mkM) − the blocker of hyperpolarization−activated cyclic nucleotide dependent cationic (HCN) -channels, or after the application of Iberiotoxin (6 nM), known blocker of the receptors of Ca++-activated high conductivity potassium channels (BKCa). The effects, produced by both blockers in AR, were less pronounced. Taken together, all these results may indicate that in electrically excitable myocardial and smooth muscle (vascular) cells, like in neural cells, ammonia causes universal activation (depolarization), implicating the group of cationic channels (HCN, BKCa, SKCa, etc.).


Key words

Keywords: myocardium, aorta, ammonium ion, coenzyme NAD+, cationic HCN channels, BKCa- channels, hyperammonemia.





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