Ventricular cardiac action potential

The ventricular cardiac action potential is characterized by five phases and is shaped by the complex interplay of a variety of Na+, Ca2+ and K+ currents (Figure 4.2). The distinct voltage-dependent properties of hERG channels [19,20] govern the time course of Ikt and the manner in which it contributes to the outward K+ current during the repolarization phase of the cardiac action potential. The opening and closing of... 

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)...

Antiarrhythmic Drugs. Figure 1 Transmembrane ionic currents of the cardiac action potential. In the middle of the figure, a typical cardiac action potential is shown as can be obtained from the ventricular myocardium (upper trace). Below, the contribution of the various transmembrane currents is indicated. Currents below the zeroline are inward currents above the zero line are outward fluxes. In the left column the name of the current is given and in the right column the possible clone redrawn and modified after [5]. 

Fig. 6. Influences of different types of antiarrhythmic agents (Vaughan-William s classification) on the shape of cardiac action potentials. First row Class I-agents action potentials of ventricular myocardial cells. Second row (from left to right) Action potential of SA-node cells influence of a )0-hlocker (class II). Action potential of ventricular myocardial cells influence of a class Ill-antiarrhythmic. Action potential of AV nodal cells influence of a class IV-antiarrhythmic (verapamil, diltiazem).

IB Lidocaine Phenytoin Tocainide Moricizine Mexiletine Minimally change V , of phase 0, decrease cardiac action potential duration, decrease inward sodium current in ventricular muscle, increase outward potassium current. 

Cardiovascular System. Atropine is sometimes used to block the effects of the vagus nerve (cranial nerve X) on the myocardium. Release of acetylcholine from vagal efferent fibers slows heart rate and the conduction of the cardiac action potential throughout the myocardium. Atropine reverses the effects of excessive vagal discharge and is used to treat the symptomatic bradycardia that may accompany myocardial infarction.4 Atropine may also be useful in treating other cardiac arrhythmias such as atrioventricular nodal block and ventricular asystole. 

Kv7.x channels encompass a gene family consisting of 5 distinct members denoted Kv7.1-Kv7.5. Kv7.1, also known as KvLQTl, is expressed primarily in non-neuronal tissues, including cardiac tissue where it contributes to repolarization of the cardiac action potential. Kv7.1 loss-of-function mutations are associated with long QT syndrome that can lead to a rare ventricular arrhythmia, torsades de pointes (Wang et al. 1996). The other members of the Kv7 family encode related potassium channels that are widely expressed... 

It is established that Ca + and K+ are involved in maintenance and termination of the plateau phase of the cardiac action potential. Furthermore, intracellular calcium concentration controls membrane K+ permeability via the various conductance components for K+ (gK], gK2, glx) (69) It is also established that action potential duration and myocardial tension development are integrally related (13). In view of previous observations and explanations for the excitation-contraction coupling process and the effects of calcium inhibitory compounds upon the cardiac action potential of ventricular muscle and Purkinje fibers, one possible explanation for the effects observed in ventricular muscle preparations is that low concentrations of calcium inhibitory compounds reduce the amount of intracellular free calcium in the vicinity of the K+ channel, thereby changing the channel s configuration resulting in a reduction in gK+ and delayed repolarization of the ventricular muscle action potential. 

Calcium overload is manifested as an early afterdepolarization of the cardiac action potential, which may result in premature depolarization of Purkinje fibers and the appearance of ventricular arrhythmias. With substantially increased calcium load, this may lead to ventricular tachyarrhythmias and death. 

Cardiac glycosides increase the influx of calcium, and decrease the outflow of potassium. Because there is little sequestration of calcium in cardiac cells, intracellular calcium may increase to toxic levels, particularly with high doses of the drug, and may exchange for sodium, via the sodium-calcium exchanger. This results in an overload of intracellular sodium and calcium, which, because of the decreased outflow of potassium, is not counterbalanced. Thus, calcium overload is manifested as an early afterdepolarization of the cardiac action potential, which may result in premature depolarization of Purkinje fibers and the appearance of ventricular arrhythmias, which may result in ventricular tachyarrhythmias and death. 

Answer A. Amiodarone is a highly effective antiarrhythmic drug, in part because of its multiple actions, which include Na channel block, beta adrenoceptor block, K channel block, and Ca channel block. Drugs that block channels (which include class lA and class III antiarrhythmics) prolong APD and ERP and predispose toward torsades de pointes ventricular arrhythmias. Flecamide is a class IC drug, lidocaine and phenytoin are class IB, and verapamil is class IV, none of which inhibits the delayed rectifier K+ current responsible for membrane repolarization during the cardiac action potential. 

A drug was tested in the electrophysiology laboratory to determine its effects on the cardiac action potential in ventricular cells. The results are shown in the diagram. Which of the following drugs does this agent most resemble ... 

A. Type la agents depress the fast sodium-dependent channel, slowing phase zero of the cardiac action potential. At high concentrations, this results in reduced myocardial contractility and excitability, and severe depression of cardiac conduction velocity. Repolarization is also delayed, resulting in a prolonged QT interval that may be associated with polymorphic ventricular tachycardia (torsade de pointes see Figure 1-7, p 15). 

Once ventricular pressure exceeds the pressure in the aorta, the aortic valve opens and systolic ejection commences (C to D). Blood flows out from the ventricle into the aorta based on the pressure gradient, the inertances, and the resistances of the outlet. The muscle continues to contract until the cardiac action potentials have run their course. 

Banyasz T, Horvath B, Jian Z, Izu LT, Chen-Izu Y (2012) Profile of L-type Ca(2+) ciurtait and Na (+)/Ca(2+) exchange current during cardiac action potential in ventricular myocytes. Heart Rhythm 9(1) 134-142... 

Compound 4 is an inhibitor of the slowly activating delayed rectifier K(+) current which repolarizes the cardiac ventricular cell membrane. As a result, the refractory period of the spontaneously contracting heart muscle is prolonged and the cardiac action potential is delayed. This helps to reduce the potentially fatal cardiac ventricular fibrillation which can result from ischaemic heart damage, leading to myocardial infarction. 

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