['To assess the late Na+ current (INalate) blockade by the combined ion channel blocker AZD1305 and its influence on repolarization liability in vitro.', 'Blockade of INalate and the peak Na+ current (INapeak) by AZD1305 and the effects of E-4031, AZD1305, and lidocaine on repolarization liability following cycle length (CL) changes were examined in dog cardiomyocytes and rabbit-superfused Purkinje fibre (PF) and ventricular muscle (VM) preparations, respectively. In the rabbit preparations, a short-long-short CL sequence was introduced during, and followed by, stimulation at a basic CL of 500 ms in the presence of E-4031, AZD1305, E-4031+AZD1305, or E-4031+lidocaine. The standard deviation of the action potential duration at 90% repolarization (APD90) of the five action potentials following resumption of the basic CL was quantified as APD90 instability. AZD1305 concentration-dependently blocked INalate (IC50=4.3 microM) and INapeak (IC50=66 microM). In PFs, E-4031, but not AZD1305, markedly prolonged APD90 (from 380+/-15 to 597+/-86 ms, P<0.05) after the long CL and augmented APD90 instability (2+/-0.4 to 24+/-6.1 ms, P<0.05), increases significantly attenuated by AZD1305 and lidocaine. In the VM, the APD90 prolongation by E-4031 was quantitatively much smaller, thus augmenting the repolarization heterogeneity between the PF and VM, an increase markedly reduced by AZD1305 and lidocaine.'] Does the combined ion channel blocker AZD1305 attenuate late Na current and IKr-induced action potential prolongation and repolarization instability?