['A high incidence of proarrhythmia has been reported with ibutilide, especially in patients with underlying heart diseases. Our previous studies have shown that extracellular acidosis and hyperkalemia attenuate the HERG-inhibitory effect of proarrhythmic drugs, e.g. quinidine, but have little impact on the less-proarrhythmic drug amiodarone. We hypothesized that ibutilide would behave like quinidine in the presence of extracellular acidosis and hyperkalemia.', 'HERG was expressed on Xenopus oocytes, and the two-electrode voltage clamp technique was employed. Our results showed that ibutilide was a potent HERG inhibitor. When extracellular solution contained 5 mM KCl and pH was 7.4, the IC(50) of ibutilide was 0.9 +/- 0.1 microM. The inhibitory effect of ibutilide was attenuated when extracellular pH decreased to 6.2. There was a significant difference in current inhibition by ibutilide at pH 7.4 versus pH 6.2 (p < 0.01). When the extracellular potassium concentration was increased from 5 to 10 mM, ibutilide produced less current inhibition, and the IC(50) was increased to 2.0 +/- 0.1 microM.'] Do extracellular acidification and hyperkalemia induce changes in HERG inhibition by ibutilide?