14th International Congress
THE "NEW FRONTIERS"
OF ARRHYTHMIAS 2000

Jan. 29 - Feb. 5, 2000
Marilleva, Trento, Italy

RT-31

Mechanisms underlying the initiation of normal and abnormal automaticity in Purkinje fibers

Mario Vassalle, Daniel E.Berg.
Department of Physiology and Pharmacology, State University of New York, Health Science Center, New York, USA

Abstract

BACKGROUND. The mechanisms of induction of normal and abnormal automaticity in Purkinje fibers and single Purkinje cells exposed in vitro to low [K⁺]_o are reviewed.

METHODS AND RESULTS. Membrane potentials were recorded by means of a microelectrode technique, and currents by means of a whole cell patch-clamp technique. The results show that in quiescent fibers low [K⁺]_o causes progressively larger oscillatory pre-potentials which attain the threshold and initiate spontaneous discharge. Drive, barium, high [Ca²⁺]_o, norepinephrine and acetylcholine have similar effects. In contrast, Cs⁺, tetrodotoxin and lidocaine suppress the oscillatory pre-potentials. In fibers driven at a slow rate, low [K⁺]_o increases the slope and amplitude of diastolic depolarization (DD), sharpens the transition between early and late diastolic depolarization, induces an after-potential at the end of early DD, and causes pre-potentials through a negative shift of an oscillatory zone during the much less affected late DD. During recovery, the cessation of activity occurs when a pre-potential misses the threshold. Lower [K⁺]_o leads to depolarization at the plateau by preventing repolarization. At depolarized levels, sub-threshold sinusoidal fluctuations initiate slow responses, which are not blocked by Cs⁺. During the recovery, a train of Cs⁺-sensitive sub- or supra-threshold oscillations appear in the oscillatory zone which is less negative than the voltage range of DD. In single Purkinje cells, low [K⁺]_o shifts the voltage-current relation of _IK1 to more negative values and allows small superimposed pulses to initiate fast inward Na⁺ transients, but only in the range of inward rectification.

CONCLUSIONS. In Purkinje fibers: 1) at polarized levels, pre-potentials occurring in the oscillatory zone are a necessary link between resting potential and threshold; 2) the pre-potentials initiate and maintain spontaneous discharge; 3) the depolarizing phase of pre-potentials is caused by a tetrodotoxin-sensitive Na⁺ component; 4) the membrane begins to oscillate when the oscillatory zone is shifted to more negative values by low [K⁺]_o (negative shift of I_K1 current-voltage relation) or the resting potential is decreased by other agents; 5) low [K⁺]_o depolarizes the membrane at the plateau by preventing phase 3 repolarization; 6) similar oscillatory phenomena occur at depolarized levels, but through a different Cs⁺-insensitive mechanism.

Key Words