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ABSTRACT: Objective
To explore the mechanisms of Kv2.1 on the secretion of ADH in rats with heart failure.Methods
In the animal study, 70 healthy male SD rats were selected. Ligation of coronary heart failure model surgery was performed in 60 rats and sham surgery was performed in the other 10 rats. Q-PCR was used to detect the mRNA expression of Kv2.1 in hypothalamus and heart. The protein expression of Kv2.1 and ADH was detected by western blot. In the cell culture study, hypothalamic neurons were cultured and divided into 7 groups. The mRNA expression of Kv2.1 and ADH was detected by Q-PCR. The protein expression of Kv2.1, CamKII, phosphorylation SynapsinI, dephosphorylation SynapsinI and ADH was detected by western blot.Results
Compared with the control group of heart failure, LVEDD, LVESD, LVEDV and LVESV were significantly decreased (P < 0.01), and LVEF and LVFS were significantly increased (P < 0.01) in the Kv2.1 agonist group; in the Kv2.1 inhibitor group, LVEDD, LVESD, LVEDV and LVESV were significantly increased (P < 0.01), and LVEF and LVFS were significantly decreased (P < 0.01). In cell culture study, after the different concentrations of Kv2.1 inhibitor gradient down the expression of Kv2.1, intracellular Ca2+ concentration gradient increased (P < 0.01), CamKII and phosphorylation of SynapsinI protein expression gradient increased (P < 0.01), dephosphorylation of SynapsinI protein expression gradient decreased (P < 0.01), and the ADH mRNA and protein expression of gradient increased (P < 0.01).Conclusions
Kv2.1 agonist can prevent the calcium overload by reducing the intracellular Ca2+ concentration, so that the phosphorylation of SynapsinI reduces and exocytosis in hypothalamic neurons is inhibited, which ease the secretion of ADH.
SUBMITTER: Li J
PROVIDER: S-EPMC5575182 | biostudies-literature | 2017
REPOSITORIES: biostudies-literature
American journal of translational research 20170815 8
<h4>Objective</h4>To explore the mechanisms of Kv2.1 on the secretion of ADH in rats with heart failure.<h4>Methods</h4>In the animal study, 70 healthy male SD rats were selected. Ligation of coronary heart failure model surgery was performed in 60 rats and sham surgery was performed in the other 10 rats. Q-PCR was used to detect the mRNA expression of Kv2.1 in hypothalamus and heart. The protein expression of Kv2.1 and ADH was detected by western blot. In the cell culture study, hypothalamic ne ...[more]