Background: The ability of dofetilide and d-sotalol to maintain their class III action during ischemia is uncertain. We investigated the effect of these two drugs on the ATP-sensitive potassium channel (IKATP), which plays a major role in ischemia-induced action potential duration shortening.
Methods and Results: The activity of (IKATP) channels was studied in excised membrane patches of single ventricular myocytes, obtained by standard enzymatic dissociation techniques from New Zealand white rabbits. Dofetilide demonstrated a dose-dependent block of (IKATP) with an EC50 of 51 ± 1 μM in inside-out patches. Its ability to block the channel was substantially less when applied to the external membrane surface. d-Sotalol significantly blocked (IKATP) (42% reduction) at a concentration of 10 μM but not at 1 μM. As with dofetilide, its ability to block (IKATP) was reduced when applied externally.
Conclusions: We conclude that dofetilide and d-sotalol block the ATP-sensitive potassium channel. but dofetilide does so only at concentrations much greater than those rcquired for block of the delayed rectifier potassium channel. d-Sotalol in contrast shows modest blockade of (IKATP) at concentrations in the tipper range of those seen during its clinical use.
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