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Abstract Objective To investigate the effect of short interfering RNAs (siRNAs) on silencing of E637K-hERG mu-tant gene and its mechanisms. Methods Western blot was used to screen specific siRNAs targeting dominant-nega-tive mutant of E637K-hERG. Whole-cel patch-clamp technique was used to examine the changes of electrical current before and after siRNA transfection. Results siRNA significantly down-regulated the expression of protein bands by interference of E637K-hERG, but not by WT-hERG. Through inhibition of WT/E637K-hERG but not WT-hERG, siRNA in-creased activation current and tail current amplitudes, shifted the activation curve and steady-state inactivation curve to-ward positive potentials by 9.62mV and 17.41mV, respectively, and reduced the velocity of channel inactivation. Conclu-sion siRNA can effectively inhibit E637K-hERG protein expression and alter the properties of WT/E637K-hERG channel current.
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