Repolarizing K⁺ currents in rabbit heart Purkinje cells

Abstract

Electrophysiological experiments on single myocytes obtained from Purkinje fibres and ventricular tissue of adult rabbit hearts were done to compare the contributions of three potassium (K+) currents to the action potentials in these two tissues. In Purkinje cells reductions in extracellular potassium, [K+]o, from normal (5.4 mM) to 2.0 mM resulted in a large hyperpolarization and marked lengthening of the action potential. In ventricular myocytes, these changes were much less pronounced. Voltage clamp measurements demonstrated that these differences were mainly due to a much smaller inward rectifier K+ current, IK1, in Purkinje cells than in ventricular myocytes. Application of 4‐aminopyridine (4‐AP, 2 mM) showed that all Purkinje cells exhibited a very substantial Ca2+‐independent transient K+ outward current, It. 4‐AP significantly broadened the early, rapid repolarization phase of the action potential. Selective inhibitors of the fast component, IK,r (MK‐499, 200 nM) and the slow component IK,s (L‐735821 (propenamide), 20 nM) of the delayed rectifier K+ currents both significantly lengthened the action potential, suggesting that these conductances are present, but very small (< 20 pA) in Purkinje cells. Attempts to identify time‐ and voltage‐dependent delayed rectifier K+ current(s) in Purkinje cells failed, although a slow delayed rectifier was observed in ventricular myocytes. These results demonstrate significant differences in action potential waveform, and underlying K+ currents in rabbit Purkinje and ventricular myocytes. Purkinje cells express a much smaller IK1, and a larger It than ventricular myocytes. These differences in current densities can explain some of the most important electrophysiological properties of these two tissues.

Ionic mechanisms of electrophysiological properties and repolarization abnormalities in rabbit Purkinje fibers

“…Both simulations using our model and previous experimental recordings (7,9) show an almost flat resting phase (rate of depolarization 0.2 mV/ms) in rabbit Purkinje cells. The lack of pacemaker activity in rabbit Purkinje cells, unlike in other species like the sheep, has been consistently shown under physiological conditions in situ in the intact cardiac wall (19), in isolated strands of Purkinje fibers (7), and also in isolated myocytes (9,10,16). Simulations were also conducted to determine the dependence of the simulated AP on stimulation rate.…”

“…The input resistance at rest was calculated as the ratio between the deflection in potential produced by injecting a small depolarizing current pulse (9). Simulation results show that injecting a 40-pA depolarizing current pulse of 500-ms duration at rest results in a 6.3-mV deflection in transmembrane potential.…”

PCP4 regulates Purkinje cell excitability and cardiac rhythmicity

“…The mechanisms responsible for this proarrhythmic propensity are incompletely understood, but compared with working ventricular myocytes (VMs), differences in T-tubular density (7), relative abundance of L and T type calcium channels (8), presence of IP 3 -sensitive Ca 2+ channels (9), greater intracellular sodium load (10), and the differential density of various repolarizing currents (11), are all considered contributory factors underlying the unique action potential (AP) and calcium-handling characteristics of PCs (12,13). Triggered mechanisms have been proposed to underlie PC-related ventricular arrhythmias, and PCs have been found to be more susceptible to both early afterdepolarizations (EADs) and delayed afterdepolarizations (DADs) compared with working VMs (5,14).…”

Small‐Conductance Calcium‐Activated Potassium Current in Normal Rabbit Cardiac Purkinje Cells

“…While there is no consensus on the neuronal origin of the PCs, there is little doubt that the PCs are electrophysiologically different than the working VMs 10. Compared with VMs, the PCs have much smaller inward rectifier K+ current and much larger Ca 2+ ‐independent transient outward K + current 26. The differences in the densities of these potassium currents in part account for the differences of the electrophysiological properties between PCs and VMs.…”