Papaverine blocks hKv1.5 channel current and human atrial ultrarapid delayed rectifier K⁺ currents

Papaverine, 1-[(3,4-dimethoxyphenyl)methyl]-6,-7-dimethoxy-isoquinoline, has been used as a vasodilator agent and a therapeutic agent for cerebral vasospasm, renal colic, and penile impotence. We examined the effects of papaverine on a rapidly activating delayed rectifier K⁺ channel (hKv1.5) cloned from human heart and stably expressed in Ltk^- cells as well as a corresponding K⁺ current (the ultrarapid delayed rectifier, I_Kur) in human atrial myocytes. Using the whole cell configuration of the patch-clamp technique, we found that papaverine inhibited hKv1.5 current in a time- and voltage-dependent manner with an IC₅₀ value of 43.4 μM at +60 mV. Papaverine accelerated the kinetics of the channel inactivation, suggesting the blockade of open channels. Papaverine (100 μM) also blocked I_Kur in human atrial myocytes. These results indicate that papaverine blocks hKv1.5 channels and native hKv1.5 channels in a concentration-, voltage-, state-, and time-dependent manner. This interaction suggests that papaverine could alter cardiac excitability in vivo.