TRANSIENT OUTWARD CURRENTS IN SUBENDOCARDIAL PURKINJE MYOCYTES SURVIVING IN THE INFARCTED HEART

Background Altered electrical activity of subendocardial Purkinje fibe rs contributes to arrhythmias in the 48-hour infarcted canine heart. C hanges in the transmembrane action potentials of these fibers include marked action potential prolongation. The ionic basis for these change s is unknown. Methods and Results We used whole-cell voltage-clamp tec hniques to study 4-aminopyridine (4-AP)-sensitive voltage-dependent tr ansient outward currents (I-to1) in Purkinje myocytes isolated from LV subendocardial (n=14) and free-running (n=15) bundles of the normal c anine heart. I-to1 in these two groups of control cells (normal-zone P urkinje cells [NZPCS]) did not differ. NZPCS I-to1 was then compared w ith I-to1 of Purkinje myocytes dispersed from subendocardium of infarc ted hearts 48 hours after total coronary artery occlusion (IZPC(48), n =14). I-to1 amplitude and current density were significantly reduced ( P<.01) in IZPC(48)s (1650+/-389 pA, 9+/-2 pA/pF) compared with NZPCS ( 2917+/-267 pA, 20.2+/-2 pA/pF) at V-t=+55 mV, V-h=-60 mV, where V-t is test potential and V-h is holding potential. Decay of I-to1 was biexp onential in all NZPCS but monoexponential in 71% of IZPC(48)s. Both NZ PCS and IZPC(48)s have a sustained 4-AP-sensitive component (at 250 ms , V-t=+55 mV: 4+/-1 pA/pF, 3+/-1 pA/pF, respectively). I-to1 voltage d ependence of inactivation did not differ between groups. In IZPC(48)s, recovery of I-to1 from inactivation was slowed significantly. Further more, significantly more I-to1 was seen with rapid pacing in NZPCS (cy cle length [CL] 5000 ms=100%, CL 1300 ms=73%, CL 330 ms=46%) than in I ZPC(48)s (CL 5000 ms=100%, CL 1300 ms=58%, CL 330 ms=31%). In three IZ PC(48)s, no I-to1 was seen at CL 330 ms. Conclusions I-to1 plays a maj or role in normal Purkinje myocyte electrophysiology, contributing bot h a large transient and a sustained component that are 4-AP-sensitive. In subendocardial Purkinje myocytes that survive in the 48-hour infar cted heart, density of I-to1 is markedly reduced and the remaining I-t o1 showed specific changes in kinetics. The alterations observed in bo th I-to1 density and function could contribute to abnormally long tran smembrane action potentials of these arrhythmogenic Purkinje myocytes of the infarcted heart.