Reduced inward rectifying and increased E-4031-sensitive K+ current density in arrhythmogenic subendocardial purkinje myocytes from the infarcted heart.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
Pinto
J M
JM
Department of Pharmacology, Columbia College of Physicians and Surgeons, New York, New York 10032, USA.
Boyden
P A
PA
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000378:metabolism* / Q000473:pathology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002586:Cesium / Q000494:pharmacology; D003627:Data Interpretation, Statistical; D004285:Dogs; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011689:Purkinje Cells / Q000187:drug effects / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D010880:Piperidines; D015221:Potassium Channels; D011725:Pyridines; C063968:E 4031; D002586:Cesium; D015761:4-Aminopyridine