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Our previous study of Chinese patients with dilated cardiomyopathy (DCM) showed that the E23K polymorphism of KATP channel was associated with the severity of ventricular arrhythmia. The present study aimed to investigate the possible mechanism underlying this phenomenon.
Transgenic rats with KK genotype were generated by genetic engineering methods. DCM was induced by intraperitoneal injection of Adriamycin (2.5mg/Kg/week for 6 weeks) in the rats. The same amount of saline serviced as control. The rats were distributed into four groups: WT-control group; KK-control group; WT-DCM group; KK-DCM group. Electrophysiology targets were recorded in vivo; conduction velocity was measured by microelectrode array technology; and the KATP channel current density was recorded by whole cell patch clamp technique.
A prolonged effect of QTc, JT interval, action potential duration (APD) and ventricle effective refractory periods(ERP) was observed after Adriamycin treatment in control groups; but the data of the rats in KK-DCM group were shortened when compared with those in WT-DCM group [QTc (229.5±15ms vs. 183±12ms, P<0.05), JT internal (67.7±3ms vs. 49.2±4ms, P<0.05), APD70 (40.63±4.51ms vs. 64.79±6.86ms, P<0.05), ERP(58.25±4.49ms vs. 47.2±4.01ms, P<0.05)]. Compared with the control groups, the DCM groups had a lower threshold of ventricular arrhythmia, more disordered conduction function, and the IKATPcurrent density was larger, and these changes were further aggravated in KK-DCM group [VFT (5.2±1.59V vs. 10.36±1.14V, P<0.05), conduction velocity(57.95±2.54cm/s vs. 78.03±8.75cm/s, P<0.05), maximal current density (17.81±1.31pA/pF vs. 13.1±1.24pA/pF, P<0.05)].
The KK genotype facilitated the activation of KATP channel, which may contribute to the shortened APD and disordered conduction function in rats with DCM, therefore increase ventricular arrhythmia of rats.