Effects And Molecular Mechanisms Of STVNa On Transient Outward Potassium Current And Calcium Currents In Rat Hypertrophic Cardiomyocytes

Cardiac hypertrophy is an initial response to various types of extracellular stress,neurohormones,growth factors and other stimulating conditions.However,persistent cardiac hypertrophy reactions eventually develop into heart failure.Therefore,it is of great significance to develop drugs and treatment methods to prevent or even reverse cardiac hypertrophy and heart failure.Isoteviol sodium(STVNa)is the sodium salt of isosteviol,which is the acid hydrolyzate of the chrysanthemide-based steviol-glycoside.The purpose of this research is to determine whether STVNa can alleviate cardiac hypertrophy of acutely isolated adult rat cardiomyocytes induced by isoprenaline and its possible mechanism.The main contents are as follows:1.Cardiac hypertrophy of acutely isolated cardiomyocytes was successfully induced by 5 μM isoprenaline(ISO).STVNa significantly decreased the cell surface area,ANP and BNP mRNA expression and meanwhile increased cell viability in hypertrophic cardiomyocytes.2.We studied the effect of STVNa on APD in cardiomyocytes.The results showed that APD20,APD50 and APD90 were significantly increased in hypertrophic cardiomyocytes compared with normal cells.STVNa decreased APD20,APD50 and APD90 in hypertrophic cardiomyocytes,which indicated that STVNa could inhibit the APD prolongation of hypertrophic cardiomyocytes.While,STVNa had no effect on the resting potential of hypertrophic cardiomyocytes.3.We studied the effect of STVNa on Ito current density of cardiomyocytes.The results showed that Ito current density was significantly decreased in hypertrophic cardiomyocytes compared with normal cells.1 μM,5 μM,10 μM and 100 μM STVNa could restore the Ito current density of hypertrophic cardiomyocytes and had a concentration-dependent effect,while 100 nM STVNa had no significant effect on Ito current density of hypertrophic cardiomyocytes.Further studies showed that STVNa cannot affect the activation and inactivation kinetic parameters of Ito current in hypertrophic cardiomyocytes.4.Next,we studied the effect of STVNa on Ca2+ currents density in cardiomyocytes.The results showed that STVNa inhibited Ca2+ currents density increase in hypertrophic cardiomyocytes.5.At last,we studied the mechanism of STVNa on Ito current density and Ca2+ current density.The results showed that the expression of Kv4.2,Kv4.3 and KCh IP2 mRNA was significantly downregulated in hypertrophic cardiomyocytes compared with normal cells,while the expression of Cav 1.2 was upregulated.The results showed that STVNa can not only significantly upregulate the mRNA expression for Kv4.2,Kv4.3 and KChIP2 in hypertrophic cardiomyocytes,but also downregulated mRNA expression for Cav1.2.Conclusion: STVNa regulates Ito current density and Ca2+ currents density in hypertrophic cardiomyocyte by regulating the expression of Kv4.2,Kv4.3,KCh IP2 mRNA and Cav1.2 mRNA respectively,thereby shortening APD.In conclusion,STVNa can alleviate myocardial hypertrophy by improving the electrophysiological properties of cardiomyocytes.