Depolarization phase, cardiac action potential

In the following, the cardiac action potential is explained (Fig. 1) An action potential is initiated by depolarization of the plasma membrane due to the pacemaker current (If) (carried by K+ and Na+, which can be modulated by acetylcholine and by adenosine) modulated by effects of sympathetic innervation and (3-adrenergic activation of Ca2+-influx as well as by acetylcholine- or adenosine-dependent K+-channels [in sinus nodal and atrioventricular nodal cells] or to dqjolarization of the neighbouring cell. Depolarization opens the fast Na+ channel resulting in a fast depolarization (phase 0 ofthe action potential). These channels then inactivate and can only be activated if the membrane is hyperpolarized... 

Figure 4.2 Cartoon representation of an ECC trace and ventricular cardiac action potential, (a) A representation of an ECC trace with its five typical deflections (PQRST) arising from the spread of electrical activitythrough the heart. The QRS wave denotes the ventricular depolarization, while the T wave represents ventricular repolarization. The QT interval therefore estimates the duration of a ventricular action potential, (b) Schematic of the five phases of a ventricular action potential. Phase 0 is the rapid depolarization phase due to a large influx of Na+ ions (Ina). Phase 1 occurs with the inactivation of Na+ channels and the onset of transient outward (repolarizing) currents (/to)...

For the ascending phases caused by the influx of cations. Navi. 5 is responsible for the initial depolarization of the action potential (phase 0). Mutations in SCN5A, the gene that encodes Navi.5, result in multiple cardiac arrhythmia syndromes [25]... 

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.]... 

Certain cardiac cells are able to initiate and maintain a spontaneous automatic rhythm. Even in the absence of any neural or hormonal input, these cells will automatically generate an action potential. They are usually referred to as pacemaker cells in the myocardium. Pacemaker cells have the ability to depolarize spontaneously because of a rising phase 4 in the cardiac action potential (see Fig. 23-1). As described previously, the resting cell automatically begins to depolarize during phase 4 until the cell reaches threshold and an action potential is initiated. 

Figure 3-2 Contribution of main ion currents (and respective genes) to time course of membrane potential changes constituting the cardiac action potential. Horizontal gray bars indicate the voltage range ion current participation in the different depolarization/repolarization phases.

The cardiac action potential can be divided into five phases, numbered 0-4. These phases result from the subsequent or parallel activity of ion channels (Figure 3.2) and/or transporters. Initially, the cell is polarized to near the electrochemical potential for potassium ions because of high K+ conductance at rest. A rapid depolarization is initiated by the activation of the fast inward Na+ current (phase 0). This depolarization is followed by a brief partial repolarization mainly resulting from the activation of the transient outward current (/t0) and the inactivation... 

The morphology of an action potential is dictated by the flow of ions across the cell membrane (Figure 2a). An inward flow of sodium and calcium ions has a depolarizing influence on the membrane potential, while an outward flow of potassium has a repolarizing effect. The upstroke of the cardiac action potential (phase 0) is due to an inward flux of sodium ions and the plateau phase (phase 2) is maintained... 

Electrical activity in the heart can be picked up by electrodes placed on the skin and recorded as the familiar electrocardiogram (ECG). The ECG is a record of the sum of all action potentials in the heart as it contracts. Action potentials are generated by depolarization followed by repolarization of the cardiac muscle cell membrane. Depolarization is initiated by an influx of sodium ions into the cardiac muscle cells, followed by an influx of calcium ions. Repolarization is brought about by efflux of potassium ions. The phases of a cardiac action potential are shown in Eigure 4.3 where the depolarization is the change in resting membrane potential of cardiac muscle cells from —90 mV to 4-20 mV. This is due to influx of sodium ions followed by influx of calcium ions. Contraction of the myocardium follows depolarization. The refractory period is the time interval when a second contraction cannot occur and repolarization is the recovery of the resting potential due to efflux of potassium ions. After this the cycle repeats itself. 

Digitalis glycosides cause an influx of extracellular calcium and an accumulation of extracellular potassium. The increased levels of extracellular potassium decrease the rate of repolarization of the cardiac cell. Thus, as levels of the drug approach the toxic range, accumulated extracellular potassium causes a lengthening of phase 3 of the cardiac action potential and an increase in the length of time between depolarizations. Thus, bradycardia is seen. 

Mechanism of action - Disopyramide is a class lA antiarrhythmic agent that decreases the rate of diastolic depolarization (phase 4), decreases the upstroke velocity (phase 0), increases the action potential duration of normal cardiac cells, and prolongs the refractory period (phases 2 and 3). It also decreases the disparity in refractoriness between infarcted and adjacent normally perfused myocardium and does not affect alpha- or beta-adrenergic receptors. 

Transmembrane action potential of a sinoatrial node cell. In contrast to other cardiac cells, there is no phase 2 or plateau. The threshold potential (TP) is -40 mV. The maximum diastolic potential (MDP) is achieved as a result of a gradual decline in the potassium conductance (gK+). Spontaneous phase 4 or diastolic depolarization permits the cell to achieve the TR thereby initiating an action potential (g = transmembrane ion conductance). Stimulation of pacemaker cells within the sinoatrial node decreases the time required to achieve the TR whereas vagal stimulation and the release of acetylcholine decrease the slope of diastolic depolarization. Thus, the positive and negative chronotropic actions of sympathetic and parasympathetic nerve stimulation can be attributed to the effects of the respective neurotransmitters on ion conductance in pacemaker cells of the sinuatrial node. gNa+ = Na+ conductance. 

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.

Actions Flecainide suppresses Phase 0 upstroke in Purkinje and myocardial fibers (Figure 17.9). This causes marked slowing of conduction in all cardiac tissue, with a minor effect on the duration of the action potential and refractoriness. Automaticity is reduced by an increase in the threshold potential rather than a decrease in the slope of Phase 4 depolarization. 

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