MECHANISM OF CLOFILIUM BLOCK OF THE HUMAN KV1.5 DELAYED RECTIFIER POTASSIUM CHANNEL

The effect of clofilium on potassium conductance was studied in excise d membrane patches from Chinese hamster ovary cells stably transfected with the Kv1.5/hPCN1 delayed rectifier K+ channel gene. Bath applicat ion of clofilium resulted in current inhibition, displaying concentrat ion-dependent acceleration of the apparent channel inactivation in bot h outside-out and inside-out patches. The steady state half-inhibition concentration in inside-out patches was 140 +/- 80 nM (n = 10), which was less than the half-inhibition concentration of 840 +/- 390 nM (n = 10) observed in outside-out patches. Clofilium accelerated apparent current inactivation but did not influence the kinetics of current act ivation or deactivation. The rate of onset of channel block induced by clofilium was not voltage dependent. In contrast, the rate of recover y from channel block was slower at more hyperpolarized membrane potent ials. Elevation of extracellular K+ levels accelerated recovery from c hannel block without influencing the rate of onset of block. These dat a suggest that clofilium may induce channel block by an ''activation t rap'' mechanism. Clofilium may be trapped near the conductivity pore s o that permeating K+ ions promote recovery from clofilium-induced bloc k.