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(Circulation. 1995;92:465-473.)
© 1995 American Heart Association, Inc.

Articles

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

Cynthia Jeck, PhD; Judith Pinto, PhD; Penelope Boyden, PhD

From the Department of Pharmacology, Columbia College of Physicians and Surgeons, New York, NY.

Correspondence to Dr Penelope A. Boyden, Department of Pharmacology, Columbia College of Physicians and Surgeons, 630 W 168th St, New York, NY 10032.

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 (IZPC₄₈, n=14). I_to1 amplitude and current density were significantly reduced (P<.01) in IZPC₄₈s (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 IZPC₄₈s. Both NZPCS and IZPC₄₈s 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 IZPC₄₈s, 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 IZPC₄₈s (CL 5000 ms=100%, CL 1300 ms=58%, CL 330 ms=31%). In three IZPC₄₈s, 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.

Key Words: potassium channels • ions • Purkinje • myocytes • myocardial infarction

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