抄録
Blockers of cardiac I kr channels encoded by HERG gene is reported as the drug clinically effective for lethal ventricular arrhythmias. However the kinetic property of a HERG channel by these blockers is not yet studied in detail. We attempted to find the characteristics. By using the standard two-microelectrode voltage clamp technique on HERG channels expressed in Xenopus oocytes, HERG blocker (nifekalant, quinidine, carvedilol, E-4031, and dofetilide) blocked HERG channels in a use-dependent manner . However, some characters were found under the block effect. Nifekalant, quinidine or carvedilol increased HERG channel current at low voltages only in the presence of a previous strong depolarizing pulse, and so this pulse could separate the facilitation effect from the block effect. On the other hand, with the facilitation effect, they caused a significant negative shift in the voltage-dependence of activation. In the case of E-4031 etc, the facilitation effect was not found. Moreover, some mutant HERG channel blocked by quinidine induced stabilization of the closed state of channel. These results reveal that each HERG blocker has a different mechanism of block effect, and has not only block effect but also other effects. [J Physiol Sci. 2006;56 Suppl:S151]
