论文部分内容阅读
The inhibitory action of diltiazem was investigated on wild-type and mutations of HERG channels, and to determine whether two aromatic residues in the S6 region were important for the blockade of IHERG by diltiazem.HERG channels (WT, Y652A and F656A) were expressed in Xenopus oocytes and studied by using standard two-microelectrode voltage-clamp technique.WT HERG is blocked in a concentration, voltage and time-dependent manner by diltiazem ([IC50] =0.581 mmol/L).After application of diltiazem, the steady state activation curve moved to the negative, but inactivation curve was positively shifted.Higher drug concentration could produce faster inhibition.However, the mutations to Ala of Y652 and F656 produced about 2-fold and 10-fold increases in IC50 for IHERG blockade, respectively.The block was decreased by Y652A and F656A.Diltiazem blocked HERG potassium channels expressed in Xenopus oocytes.Mutations of Y652A and F656A lightly decreased the blockade of diltiazem.