Reduced inward rectifying and increased E-4031-sensitive K+ current density in arrhythmogenic subendocardial purkinje...

Subendocardial Purkinje myocytes from the 48-hour infarcted heart (IZPCs) have reduced resting potentials, possibly due to altered inwardly rectifying K+ currents IK1. Abnormal depolarization-activated outward K+ currents could contribute to long triangularly shaped action potentials of IZPCs.

We used whole cell patch recordings to compare cesium-sensitive IK1 and 4-aminopyridine (4-AP)-resistant, noninactivating sustained IK between normal Purkinje myocytes (NZPCs) and IZPCs. IZPCs showed decreased net membrane currents. Two IZPC groups were distinguished, based on 4-AP-resistant outward K+ currents. IZPC-I had isochronal IK1 current-voltage relations similar to NZPCs whereas IZPC-II showed significantly reduced IK1 and increased outward plateau currents. To study the sustained IK in the presence of the Class III antiarrhythmic agent E-4031, a two-pulse protocol was used to inactivate transient outward currents, followed by step depolarizations. E-4031-sensitive currents were significantly greater in IZPCs at depolarized potentials (> 0 mV). Similar to NZPCs, IZPC E-4031 currents showed time dependence during depolarization, lack of rectification at positive steps, and voltage-dependent recovery from block.

Decreased IK1 may account for reduced resting potentials in IZPCs. E-4031-sensitive currents in NZPCs, unlike those in canine ventricular myocytes, are sensitive to 4-AP and are larger in IZPCs.