External nickel blocks human Kv1.5 channels stably expressed in CHO cells

We have investigated the actions of Nickel (Ni2+) on a human cardiac potass ium channel (hKv1.5), the main component of human atrial ultra-rapid delaye d rectifier current, stably expressed in Chinese hamster ovary cell line us ing the whole-cell voltage-clamp technique. External Ni2+ reversibly decrea sed the amplitude of the current in a concentration-dependent manner. The c oncentration for half-maximum inhibition of the current at +50 mV was 568 m um. The activation, deactivation, reactivation kinetics of the current were not affected by Ni2+. Block was not voltage-dependent but frequency-depend ent block was apparent. The extent of channel block during the first pulse increased when the duration of exposure to Ni2+ prior to channel activation , was prolonged indicating that Ni2+ interacted with hKv1.5 in the closed s tate. The percentage of current remaining in presence of Ni2+ decreased ste eply over the range of steady-state channel inactivation, consistent with a n enhanced block with increased inactivation. This suggests that Ni2+ prefe rentially blocks nonconducting hKv1.5 channels, either in the resting or in activated state in a concentration-dependent manner. The data indicate that the mechanisms of hKv1.5 channel inhibition by Ni2+ are distinct from thos e of other K+ channels.