Abstract
Background Nifekalant, a blocker of cardiac delayed rectifier K+ current (IKr) channels encoded by a human ether-a-go-go related gene (HERG), is reported as the drug clinically effective for lethal ventricular tachyarrhythmias. But the kinetic properties of nifekalant on HERG channels are not studied sufficiently. So we attempted to analyze in detail the properties and find the characteristics. Methods and Results By using the standard two-microelectrode voltage clamp technique on HERG channels expressed in Xenopus oocytes, nifekalant blocked HERG channels in a use-dependent and non frequency-dependent manner, and caused a negative shift of the voltage-dependence of activation. Nifekalant 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. Without the facilitation effect, nifekalant blocked HERG channel current in a weak voltage-dependent manner. On the other hand, with the facilitation effect, nifekalant caused a significant negative shift in the voltage-dependence of activation. In the case of E-4031, a methanesulfonanilide anti-arrhythmic drug, the facilitation effect was not found. Conclusions The strong depolarizing prepulse allows nifekalant to increase the HERG channel currents, and the facilitation effect might be the unique characteristic of nifekalant. [Jpn J Physiol 55 Suppl:S128 (2005)]
