Purkinje cell action potential

Recently, Llinas and Sugimori (1980a) have described the use of a completely different bath similar to that first described by Okamoto and Quastel (1971 ) and Yamamoto (1974) which not only allows long-term intracellular recording from Purkinje cell dendrites, but allows direct visualization of the impalement site, whether somatic or dendritic. In addition, their extremely careful experimental dissection of the ionic basis of the Purkinje cell action potential shows that fast and effective changes of the incubation media can be made. 

Disopyramide administration reduces membrane responsiveness in Purkinje fibers and ventricular muscle and reduces the action potential amplitude. Even greater depression may occur in damaged or injured myocardial cells. Action potentials are prolonged after disopyramide administration, and this results in an increase in the ERPs of His-Purkinje and ventricular muscle tissue. Unlike procainamide and quinidine, disopyramide does not produce postrepolarization refractoriness. 

FIGURE 23-1 T The cardiac action potential recorded from a Purkinje cell. The effective refractory period is the time during which the cell cannot be depolarized, and the relative refractory period is the time in which a supranormal stimulus is required to depolarize the cell. Action potential phases [0-4] and the ionic basis for each phase are discussed in the text. From Keefe DLD, Kates RE, Harrison DC. New antiarrhythmic drugs their place in therapy. Drugs. 1981 22 363 with permission.]... 

Procainamide (Class IA antiarrhythmic drug) is an effective agent for ventricular tachycardia. Its mechanism of action involves blockade of the fast Na+ channels responsible for phase 0 in the fast response tissue of the ventricles. Therefore, its effect is most pronounced in the Purkinje fibers. The effects of this drug s activity include a decrease in excitability of myocardial cells and in conduction velocity. Therefore, a decrease in the rate of the phase 0 upstroke and a prolonged repolarization are observed. As a result, duration of the action potential and the associated refractory period is prolonged and the heart rate is reduced. These effects are illustrated by an increase in the duration of the QRS complex. 

The electrical impulse for contraction (propagated action potential p. 136) originates in pacemaker cells of the sinoatrial node and spreads through the atria, atrioventricular (AV) node, and adjoining parts of the His-Purkinje fiber system to the ventricles (A). Irregularities of heart rhythm can interfere dangerously with cardiac pumping func-tioa... 

Mechanism of Action An antiarrhythmic that shortens duration of action potential and decreases effective refractory period in the His-Purkinje system of the myocardium by blocking sodium transport across myocardial cell membranes. Therapeutic Effect Suppresses ventricular arrhythmias. 

Mechanism of Action An antiarrhythmicthat prevents sodium current across myocardial cell membranes. Has potent local anesthetic activity and membrane stabilizing effects. Slows AV and His-Purkinje conduction and decreases action potential duration and effective refractory period. Therapeutic Effect Suppresses ventricular arrhythmias. 

Schematic representation of the heart and normal cardiac electrical activity (intracellular recordings from areas indicated and ECG). Sinoatrial (SA) node, atrioventricular (AV) node, and Purkinje cells display pacemaker activity (phase 4 depolarization). The ECG is the body surface manifestation of the depolarization and repolarization waves of the heart. The P wave is generated by atrial depolarization, the QRS by ventricular muscle depolarization, and the T wave by ventricular repolarization. Thus, the PR interval is a measure of conduction time from atrium to ventricle, and the QRS duration indicates the time required for all of the ventricular cells to be activated (ie, the intraventricular conduction time). The QT interval reflects the duration of the ventricular action potential.

Lidocaine blocks activated and inactivated sodium channels with rapid kinetics (Figure 14-9) the inactivated state block ensures greater effects on cells with long action potentials such as Purkinje and ventricular cells, compared with atrial cells. The rapid kinetics at normal resting potentials result in recovery from block between action potentials and no effect on conduction. The increased inactivation and slower unbinding kinetics result in the selective depression of conduction in depolarized cells. 

When I started as a novice in the field of cardiac electrophysiology, the dogma was that gap junctions are specialized membrane structures present in the cardiac and smooth muscle of vertebrates where they serve to propagate the action potential from cell to cell. Purkinje fibers and muscular trabeculae were the preferred cardiac preparations. These multicellular preparations were suitable to perform cable analyses and diffusion studies. At that time, my mentor, Silvio Weidmann, had already accomplished his elegant functional studies. 

Figure 30-15 (A) Diagram of the two-dimensional tree formed by dendrites of a single Purkinje cell of the cerebellum. From Llinas.404 (B) Schematic diagram showing input and output pathways for Purkinje cells. (C) Recordings of output from four different neurons of the inferior olive. These action potentials are thought to arise from oscillations that arise within the neurons or within arrays of adjacent neurons coupled by electrical (gap junction) synapses. These oscillations synchronize the generation of action potentials so that some cells oscillate in synchrony while others (e.g., cell 4 above) do not. From McCormick.412...

The action potential recorded from a cardiac Purkinje fiber is shown in Figure 23-1. At rest, the interior of the cell is negative relative to the cell s exterior. As in other excitable tissues (neurons, skeletal muscle), an action potential occurs when the cell interior suddenly becomes positive (depolarizes), primarily because of sodium ion influx. The cell interior then returns to a negative potential (repolarizes), primarily because of... 

The number of sodium channels available for activation determines the conduction velocity of the action potential in cardiac cells. The more sodium channels available for activation, the faster the conduction velocity occurs. At resting membrane potential of ventricular, atrial, and Purkinje cells (-85 mV), the m gate is closed, preventing any influx of sodium therefore, no action potential develops (Resting). With an... 

Fig. 24.1 The action potential of a cardiac cell that is capable of spontaneous depolarisation (SA or AV nodal, or His-PurkInje) indicating phases 0-4 the figure illustrates the gradual increase in transmembrane potential (mV) during phase 4 cells that are not capable of spontaneous depolarisation do not exhibit increase in voltage during this phase (see text).The modes of action of antiarrhythmic drugs of classes I, II, III and IV are indicated in relation to these phases...

Mexiletine hydrochloride, like cla.ss I antiarrhythmic agents, blocks the fast Na channel in cardiac cells. It is especially effective on the Purkinje fibers in the heart. The drug increases the threshold of excitability of myocardial cells by reducing the rale of rise and amplitude of the action potential and decreases aulomaliciiy. 

Standard microelectrode techniques were used to study the effects of isocorydine on potential characteristics of canine cardiac Purkinje fibers and ventricular myocardium in vitro. In the Purkinje fibers, the action potential durations APDjj and APD were prolonged at 3 pmol/1 but shortened at 30 pmol/1 by isocorydine. The action potential amplitude and maximal upstroke velocity were decreased at 100 pmol/1. In the ventricular myocardium, the action potential characteristics were changed by isocorydine at concentrations above 30 pmol/1. The APDJ0 was shortened, the APD90 was prolonged, and the maximal upstroke velocity was decreased at 30 pmol/1. The effective refractory period was prolonged by the alkaloid in Purkinje fibers and ventricular myocardium. These results indicated that the alkaloid may interfere with K+, Na+, and Ca+2 currents in myocardial cell membranes at different concentrations [287]. 

Figure 27F-1 Calcium transients in a cerebellar Purkinje cell. The image on the right is of the cell filled with a fluorescent dye that responds to the calcium concentration. Fluorescent transients are shown on the top left recorded at areas d, p, and s in the cell. The transients in region d correspond to the dendrite region of the cell. Specific calcium signals can be correlated to the action potentials shown on the bottom left. (From V. Lev-Ram, H. Mikayawa, N. Lasser-Ross, W. N. Ross, J. Neurophysiol. 1992, 68. 1170. With permission of the American Physiological Society.)...

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