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Dioscin improves heart function by increasing sodium influx via NCX in rat cardiomyocytes
Author(s) -
Yin Yongqiang,
Cong Tianshen,
Yang Fan,
Han Yu,
Wen Ke,
Kang Yi,
Lou Jianshi
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.732.2
Subject(s) - preload , ventricular pressure , ventricle , medicine , inotrope , calcium , sodium calcium exchanger , sodium , cardiology , perfusion , endocrinology , chemistry , calcium in biology , cardiac function curve , contractility , blood pressure , hemodynamics , heart failure , organic chemistry
Objective Dioscin (Dio) is widely used for the treatment of ischemic heart disease in China. The molecular mechanism underlying the inotropic effects of Dio, however, remains poorly understood. Methods and Results Left ventricle contractile function was measured using the Langendorff non‐recirculating mode of isolated rat heart perfusion. Effects of Dio on cardiac function were assessed by measuring left ventricular systolic pressure (LVSP) and left ventricular end diastolic pressure (LVEDP) as well as the peak rate of rise/fall of left ventricular pressure (±dP/dtmax), in absence or presence of a sodium‐calcium exchanger inhibitor SEA0400. Our ex vivo data show that within the concentrations of 0.1–1μmol/L, Dio significantly increased the LVSP and +dP/dtmax, and these effects were significantly antagonized by 1 μmol·L −1 SEA0400. Furthermore, we investigated the effect of Dio on sodium current (I Na ) and L‐type calcium current (I Ca,L ). Intriguingly, the I Ca,L was found to be inhibited by Dio, while the I Na was augmented by Dio. The effect of Dio on contractile function and I Ca,L appears to be contradictory. Therefore, we assessed the effect of Dio on the [Ca 2+ ] i in H9c2 cells. Dio significantly increases the relative fluorescence intensity of intracellular calcium (n=8, P<0.01 vs control), which was partially attenuated by either SEA0400 or calcium‐free or sodium‐free extracellular fluid. Mitochondrial membrane potential was further detected with multifunctional microplate reader in order to determine whether Dio causes mitochondrial injuries. Our data show that Dio barely affected the mitochondrial membrane potential at the concentration of 0.1–1 μmol·L −1 , while 10 μmol·L −1 dioscin results in a slight decrease in the mitochondrial membrane potential. Conclusion Our results demonstrate that Dio exerts the positive inotropic effect through elevating [Ca 2+ ] i and increasing sodium influx and sodium‐calcium exchange via the Na + /Ca 2+ exchanger (NCX) in rat cardiomyocytes. Support or Funding Information Supported by Youth Project of Tianjin Natural Fundation (14JCQNJC13700) to Yongqiang Yin