Modulation of the transducer function of Na super(+),K super(+)-ATPase : new mechanism of heart remodeling

• Published in: Canadian journal of physiology and pharmacology 2016-01, Vol.94 (10), p.1110-1116
• Main Authors: Lopatina, Ekaterina V, Kipenko, Anna V, Pasatetskaya, Natalia A, Penniyaynen, Valentina A, Krylov, Boris V
• Format: Article
• Language: English
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/cjpp-2015-0577

Endogenous digitalis-like factors were found in the mammalian and human blood. It was the starting point for the elucidation of the new non-pumping function of the Na super(+),K super(+)-ATPase . It was previously well known that Na super(+),K super(+)-ATPase is a pharmacological target receptor for cardiac glycosides (J.C. Skou. 1957. Biochim. Biophys. Acta, 23: 394-401). We have investigated the trophotropic effects of such agents as ouabain, epinephrine, norepinephrine, atenolol, and comenic acid using the organotypic tissue culture combined with the reconstruction of optical cross sections and confocal microscopy. It was shown that the growth zone of organotypic culture forms a multidimensional structure. Our results indicate that the cardiac glycoside ouabain applied in endogenous concentrations (10 super(-8), 10 super(-10) mol/L) can modulate transducer function of Na super(+),K super(+)-ATPase and control the cell growth and proliferation. It was also shown that Src-kinase is involved in "endogenous" ouabain activated intracellular pathways as a series unit. Epinephrine (10 super(-9)-10 super(-14) mol/L) and comenic acid (10 super(-6)-10 super(-10) mol/L) were demonstrated to modulate the growth of 10- to 12-day-old chicken embryo cardiac tissue explants in a dose-dependent manner. Epinephrine and comenic acid regulate growth and proliferation of the cardiac tissue via receptor-mediated modulation Na super(+),K super(+)-ATPase as a signal transducer. The trophotropic effects of the investigated agents specifically control the heart remodeling phenomenon.Original Abstract: Des facteurs endogenes ressemblant a la digitale ont ete decouverts dans le sang de mammiferes et d'humains. Voila le point de depart de l'elucidation d'une nouvelle fonction de l'enzyme Na super(+),K super(+)-ATPase ou elle ne jouerait pas le role de pompe. On savait deja tres bien que la Na super(+),K super(+)-ATPase est un recepteur pharmacologique cible par les glycosides cardiaques (J.C. Skou. 1957. Biochim. Biophys. Acta, 23: 394-401). A l'aide de cultures tissulaires organotypiques avec reconstruction de coupes transversales optiques et de la microscopie confocale, nous avons etudie les effets trophotropes de tels agents que l'ouabaine, l'epinephrine, la norepinephrine, l'atenolol et l'acide comenique. Nous avons observe que la zone de croissance de la culture organotypique forme une structure multidimensionnelle. Nos resultats montrent que l'exposition a l'ouabaine, le glyc