Oscillatory Zones and Their Role in Normal and Abnormal Sheep Purkinje Fiber Automaticity

Abstract

The mechanisms by which low [K⁺]_o induces spontaneous activity was studied in sheep Purkinje fibers. Purkinje strands were superfused in vitro and membrane potentials were recorded by means of a microelectrode technique. The results show that low [K⁺]_o increases the slope and amplitude of early diastolic depolarization, sharpens the transition between early and late diastolic depolarizations, induces an after-potential and large pre-potentials through a negative shift of an oscillatory zone. Pre-potentials occur progressively sooner during diastole and merge with the after-potential to induce uninterrupted spontaneous discharge. During recovery, when the rate slows, after- and pre-potentials separate once more, the slower discharge decreasing the after-potentials but not the pre-potentials. Low [K⁺]_o has little effect on the plateau, but markedly slows phase 3 repolarization and may altogether prevent it. At depolarized levels, voltage oscillations, slow responses, sinusoidal fluctuations or quiescence may be present depending on voltage. During the recovery, a train of either sub-threshold oscillations or spontaneous action potentials appear towards the end of phase 3 repolarization. The cessation of the action potentials unmasks large sub-threshold oscillations, that occur in the oscillatory zone. Drive, high [Ca²⁺]_o and norepinephrine increase slope and amplitude of early diastolic depolarization as low [K⁺]_o does. In low [K⁺]_o, Cs⁺ prevents spontaneous discharge at polarized levels, but not the decrease in resting potential nor the onset of slow responses at depolarized levels. Cs⁺ blocks the train of oscillations and of action potentials occurring during recovery. We conclude that low [K⁺]_o steepens early diastolic depolarization and increases its amplitude through an after-potential that results from an increased Ca²⁺ load; allows the attainment of the threshold through Cs⁺-sensitive voltage oscillations which develop when the oscillatory zone is entered either by diastolic depolarization or by phase 3 repolarization; and causes voltage oscillations also at depolarized levels, but through a Cs⁺-insensitive different mechanism.

Patch-clamp analysis in canine cardiac Purkinje cells of a novel sodium component in the pacemaker range

“…Instead, when [K + ] o is suitably lowered, the initiation of spontaneous discharge is characterised by the fact that the resting potential undergoes progressively larger voltage oscillations (Th V os : the voltage oscillations near the threshold for the upstroke; Spiegler & Vassalle, 1995). The depolarising phase of a Th V os eventually attains the threshold potential (Vassalle, 1965; Spiegler & Vassalle, 1995; Berg & Vassalle, 2000) and initiates spontaneous discharge.…”

“…As the low [K + ] o perfusion continues, the voltage range of Th V os (‘oscillatory zone’) shifts to more negative values, Th V os occur progressively sooner during diastole, and eventually Th V os fuse with the early diastolic depolarisation (DD 1 ): at that time, DD appears to directly continue into the upstroke of the action potential (Berg & Vassalle, 2000). However, that the depolarising phase of Th V os (not DD) is responsible for the attainment of the threshold even when Th V os are no longer visible is suggested by fact that when [K + ] o is increased again, the failure of the membrane potential to attain the threshold unmasks Th V os (see Fig.…”

“…However, that the depolarising phase of Th V os (not DD) is responsible for the attainment of the threshold even when Th V os are no longer visible is suggested by fact that when [K + ] o is increased again, the failure of the membrane potential to attain the threshold unmasks Th V os (see Fig. 7 in Vassalle, 1977) which gradually decrease in size until a steady resting potential is attained (Berg & Vassalle, 2000). Therefore, a TTX‐sensitive component appears to be an essential part of Th V os and to be required for both initiation and maintenance of discharge in Purkinje fibres.…”

Voltage-Independent Calcium Channels, Molecular Sources of Supraventricular Arrhythmia

“…Abnormal automaticity occurs when ectopic sites in the atria (or ventricle) spontaneously depolarize independently of normal sinus rhythm or without a preceding triggering event. Investigators like Vassalle [65] have made important contributions to our current understanding of this type of ectopy. Typical abnormal automaticity occurs during hypoxia and ischemia when myocytes partially depolarize from their resting potential of ~-85 to about -65mV.…”

Biomedical Vignette

“…Purkinje fibers differ from the sinoatrial node in several respects, including the presence of ionic currents during diastolic potentials and the range of pacemaker potential [17]. Berg and Vassalle [1] identified in sheep Purkinje fibers the existence of potential ranges (oscillatory zones) when this subsidiary pacemaker is superfused with low [K] 0 . Cs + prevents spontaneous discharge at polarized levels, but not the decrease in resting potential nor the onset of slow responses at depolarized levels.…”