title: Effect of Dofetilide and d-Sotalol on the ATP-Sensitive Potassium Channel of Rabbit Ventricular Myocytes.
abstract: 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 (I(KATP)), which plays a major role in ischemia-induced action potential duration shortening. METHODS AND RESULTS: The activity of I(KATP) 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 I(KATP) with an EC(50) 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 I(KATP) (42% reduction) at a concentration of 10 µM but not at 1 µM. As with dofetilide, its ability to block I(KATP) 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 required for block of the delayed rectifier potassium channel. d-Sotalol in contrast shows modest blockade of I(KATP) at concentrations in the upper range of those seen during its clinical use.
authors.affiliation: Departments of Cardiology, Victor Chang Cardiac Research Institute, Sydney, New South Wales, Australia
authors.initials: PD
authors.lastname: West
authors.initials: JA
authors.lastname: Bursill
authors.initials: KR
authors.lastname: Wyse
authors.initials: DK
authors.lastname: Martin
authors.initials: TJ
authors.lastname: Campbell