| Part IAn experimental study of the dynamic changes of expression ofpotassium channels Kv2.1 in post- myocardial infarction rat heart.Objective To investigate the dynamic changes of the expression of potassium channel Kv2.1 in post-myocardial infarction (MI) rat heart.Methods Using a rat model of MI, induced by the left anterior descending coronary artery (LAD) ligation in female Sprague-Dawley rats, the living rats were enrolled into post-MI group. Accordingly, the sham-operation group (sham-group) was established. According to the time of getting sample, the living rats in each group were divided into two subgroups (7 days group and 30 days group). Using semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and western blots, we measured mRNA and channel protein of Kv2.1 in each group. Results Compared to the sham-group, Kv2.1 mRNA and channel protein in the post-MI group remarkably decreased regardless of 7 days or 30 days (P<0.05 or P<0.01). Compared to the 7 days post-MI group, Kv2.1 mRNA and protein in the 30 days post-MI group remarkably reduced (P<0.05).Conclusion The expression of potassium channels Kv2.1 after myocardial infarctionexhibits the time-dependent downregulation, which may be one of the molecularmechanisms that are able to cause the arrhythmia after myocardial infarction.Part IIEffects of valsartan on the changes of expression of potassium channels Kv2.1 in post-myocardial infarction ratObjective To study the effects of valsartan on the changes of the expression of potassium channels Kv2.1a-subunit of left ventricular non-infarcted myocardiums in post-myocardial infarction (post-MI) rats.Methods Using a rat model of MI, induced by the left anterior descending coronary artery (LAD) ligation in female Sprague-Dawley rats, the living rats were randomly divided into post-MI group( 7 days group[n=10]; 30 days group[n=11]) or valsartan group(7 days group[n=10]; 30 days group[n=10]; valsartan 30mg.kg-1.day-1). Accordingly, the sham-operation group (sham-group) was established. Using semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and western blots, we measured the contents of Kv2.1 mRNA and protein in each group. Results Compared to sham-groups, the expression levels of Kv2.1 mRNA and protein in the post-MI group prominently reduced on 7 days (P<0.05) or 30 days (P＜0.01). Compared to Post-MI groups, the expression levels of Kv2.1 mRNA and protein in the valsartan groups increased remarkably on 7 days (P<0.05) or 30 days (P<0.01). There were no differences between the sham-groups and the valsartan groups (P>0.05).Conclusion Valsartan may reverse the downregulation of expression of potassium channels Kv2.1 in post-myocardial infarction rat markedly, which suggests that angiotensin II signaling pathway can be one of major signaling-transduction pathway bringing potassium channel Kv2.1 α-subunit downregulation.Part IIIEffects of valsartan on the gene expression of protein kinase Cisoform, Giα-2, and β-adrenergic receptor kinase-1 inpost-myocardial infarction ratObjective To study the effects of valsartan on the gene expression of protein kinase C isoforms (PKC-ε), Giα-2, and β-adrenergic receptor kinase-1 and to explore the molecular mechanism of valsartan modulating the changes of potassium channel Kv2.1 in post-myocardial infarction rat heart.Methods Using a rat model of MI, induced by the left anterior descending coronary artery (LAD) ligation in female Sprague-Dawley rats, the living rats were randomly divided into post-MI group( 7 days group[n=10]; 30 days group[n=11]) or valsartan group(7 days group[n=10]; 30 days group[n=10]; valsartan 30mg.kg-1.day-1). Accordingly, the sham-operation group (sham-group) was established. Using semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), we measured the contents of protein kinase C isoforms (PKC-ε), Giα-2, and β-adrenergic receptor kinase-1 mRNA in each group.Results Compared to sham-groups, the expression levels of protein kinase C isoforms (PKC-ε), Giα-2, and β-adrenergic receptor kinase-1 mRNA in the post-MI group prominently increased on 7 days (P＜0.05) or 30 days (P<0.01). Compared to Post-MI groups, the expression levels of protein kinase C isoforms (PKC-ε), Giα-2, and β-adrenergic receptor kinase-1 mRNA in the valsartan groups reduced remarkably on 7 days (P＜0.05) or 30 days (P<0.01). There were no differences between the sham-groups and the valsartan groups (P>0.05).Conclusion The gene expressions of protein kinase C isoforms (PKC-ε), Giα-2, and β-adrenergic receptor kinase-1 are up-regulated remarkably in Post-MI rat heart; Valsartan may normalize these changes prominently, which can be the molecular mechanism of valsartan modulating the changes of potassium channel Kv2.1 in post-myocardial infarction rat.
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