Prolonged duration of repolarization and decreased conduction velocity in the atrial myocardium after hypothermic ischemia-reperfusion may be related to expressions of inward rectifier potassium channel 2.1 protein and connexin 40

Abstract

<jats:sec><jats:title>Objectives:</jats:title><jats:p> The study aimed to determine the role of inward rectifier potassium channel 2.1 protein and connexin 40 expressions in regulating the duration of repolarization and conduction velocity of right atrial myocardium in rats following hypothermic ischemia-reperfusion. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> The Langendorff isolated rat cardiac perfusion models were divided into control (C) and hypothermic ischemia-reperfusion groups, with 8 models in group C and 16 models in group ischemia-reperfusion. Depending on the incidence of atrial arrhythmia after reperfusion, the models in group ischemia-reperfusion were further divided into reperfusion non-atrial arrhythmia or reperfusion atrial arrhythmia subgroup. Right atrial monophasic action potential duration at 50% and 90% of repolarization after 30 minutes of continuous perfusion in group C and group ischemia-reperfusion (T<jats:sub>0</jats:sub>), 105 minutes of continuous perfusion in group C or after 15 minutes of reperfusion in group ischemia-reperfusion (T<jats:sub>1</jats:sub>) and 120 minutes of continuous perfusion in group C or 30 minutes of reperfusion in group ischemia-reperfusion (T<jats:sub>2</jats:sub>) were recorded. Right atrial conduction velocity and effective refractory period were recorded at T<jats:sub>2</jats:sub>. Then, the expressions of inward rectifier potassium channel 2.1 protein and connexin 40 in the right atrial myocardium were detected. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> Monophasic action potential duration at 50% and 90% were higher at T<jats:sub>1</jats:sub> and T<jats:sub>2</jats:sub> than those at T<jats:sub>0</jats:sub> in subgroup reperfusion atrial arrhythmia (p &lt; 0.05); monophasic action potential duration at 50% in subgroup reperfusion atrial arrhythmia were larger than group C and subgroup reperfusion non-atrial arrhythmia at T<jats:sub>1</jats:sub> and T<jats:sub>2</jats:sub> (p &lt; 0.05); monophasic action potential duration at 90% in subgroup reperfusion atrial arrhythmia were larger than group C and subgroup reperfusion non-atrial arrhythmia at T<jats:sub>1</jats:sub> and T<jats:sub>2</jats:sub> (p &lt; 0.05); effective refractory period in subgroup reperfusion atrial arrhythmia was greater than that in group C and subgroup reperfusion non-atrial arrhythmia, and the conduction velocity and the expressions of inward rectifier potassium channel 2.1 protein and connexin 40 were significantly lower than group C and subgroup reperfusion non-atrial arrhythmia (p &lt; 0.05). </jats:p></jats:sec><jats:sec><jats:title>Conclusions:</jats:title><jats:p> The prolonged duration of repolarization and a decrease in conduction velocity of the atrial myocardium occur in rats after hypothermic ischemia-reperfusion. These observed effects may be related to the downregulated expressions of connexin 40 and inward rectifier potassium channel 2.1. </jats:p></jats:sec>

Nkx2.5: a crucial regulator of cardiac development, regeneration and diseases

“…Related experiments have shown that the connexin 40 promoter has a binding site for Nkx2.5, and in vivo transcriptional activation studies have shown that Nkx2.5 can activate the expression of the connexin 40 promoter ( 115 ). What's more, mutations in the Nkx2.5 gene lead to apoptosis of autorhythmic cells, which may also be the cause of the arrhythmia ( 115 ). 15% of patients with sudden cardiac death have inherited atrial septal defect and atrioventricular block ( 116 ).…”