Transient Outward Currents in Subendocardial Purkinje Myocytes Surviving in the Infarcted Heart

Abstract

Background Altered electrical activity of subendocardial Purkinje fibers contributes to arrhythmias in the 48-hour infarcted canine heart. Changes in the transmembrane action potentials of these fibers include marked action potential prolongation. The ionic basis for these changes is unknown. Methods and Results We used whole-cell voltage-clamp techniques to study 4-aminopyridine (4-AP)–sensitive voltage-dependent transient outward currents (I to1 ) in Purkinje myocytes isolated from LV subendocardial (n=14) and free-running (n=15) bundles of the normal canine heart. I to1 in these two groups of control cells (normal-zone Purkinje cells [NZPCS]) did not differ. NZPCS I to1 was then compared with I to1 of Purkinje myocytes dispersed from subendocardium of infarcted 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 biexponential in all NZPCS but monoexponential in 71% of IZPC 48 s. Both NZPCS 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 dependence of inactivation did not differ between groups. In IZPC 48 s, recovery of I to1 from inactivation was slowed significantly. Furthermore, significantly more I to1 was seen with rapid pacing in NZPCS (cycle length [CL] 5000 ms=100%, CL 1300 ms=73%, CL 330 ms=46%) than in IZPC 48 s (CL 5000 ms=100%, CL 1300 ms=58%, CL 330 ms=31%). In three IZPC 48 s, no I to1 was seen at CL 330 ms. Conclusions I to1 plays a major role in normal Purkinje myocyte electrophysiology, contributing both a large transient and a sustained component that are 4-AP–sensitive. In subendocardial Purkinje myocytes that survive in the 48-hour infarcted heart, density of I to1 is markedly reduced and the remaining I to1 showed specific changes in kinetics. The alterations observed in both I to1 density and function could contribute to abnormally long transmembrane action potentials of these arrhythmogenic Purkinje myocytes of the infarcted heart.