Abstract: AIM:To examine the effects of diltiazem, an L-type Ca2+ channel blocker, on the activation and inactivation kinetics of fKv1.4, a potassium channel that generates the cardiac transient outward potassium current. METHODS: cRNA of fKv1.4ΔN, an N-terminal deleted mutant of the ferret Kv1.4 potassium channel, was injected into Xenopus oocytes to express the fKv1.4ΔN channel in cells. Currents were recorded using a two-electrode voltage clamp technique. RESULTS: Diltiazem (10 μmol/L to 1 000 μmol/L) blocked the fKv1.4ΔN channel in a frequency-dependent, voltage-dependent and concentration-dependent manner, suggesting an open channel block. IC50 was (241.04±23.06) μmol/L for fKv1.4Δ N channel at +50 mV. After application of diltiazem, fKv1.4 ΔN inactivation was bi-exponential, with a faster portion (drug-induced inactivation) and a slower portion (C-type inactivation). Diltiazem increased C-type inactivation rate. However, diltiazem did not shift fKv1.4ΔN steady activation curves. CONCLUSION: Diltiazem accelerates the inactivation of Kv1.4ΔN channel by binding to the open state of the channel.