Depolarization-repolarization

Depolarization Repolarization Resting Stage Active Stage Resting Stage... 

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.

Pharmacology and Mechanism of Action. Proposed mechanisms inclnde alteration of ion flnxes associated with depolarization, repolarization, and membrane stability alteration of calcium uptake in presynaptic terminals influence on calcium-dependent synaptic protein phosphorylation and transmitter release alteration of the sodium-potassinm ATP-dependent ionic membrane pump and prevention of cyclic nucleotide buildup and cerebellar stimulation. ... 

Depolarization as described above occurs in a single region of a nerve fiber. Transmission of the signal along the fiber occurs because the influx of sodium and efflux of potassium in one section of the fiber causes similar disturbances in adjacent regions of the fiber and the depolarization/repolarization proceeds down the fiber quickly. The traveling pulse is called the action potential. Typical speeds are from 1 to 100 meters per second. 

The mechanism whereby cardiac glycosides cause a positive inotropic effect and electrophysiological changes is still not completely known despite years of active investigation. Several mechanisms have been proposed, but the most widely accepted mechanism involves the ability of cardiac glycosides to inhibit the membrane-bound Na /K -adenosine triphosphatase (Na /K -ATPase) pump responsible for sodium/potassium exchange. To understand better the correlation between the pump and the mechanism of action of cardiac glycosides on the heart muscle contraction, one has to consider the sequence of events associated with cardiac action potential that ultimately leads to muscular contraction. The process of membrane depolarization/repolarization is controlled mainly by the movement of the three ions, Na", K", Ca ", in and out of the cell. 

Keywords Cardiac Ioti channels Depolarization Repolarization Arrhythmias... 

Neural Excitation of Muscle. Voluntary contraction of human muscle initiates in the frontal motor cortex of the brain, where impulses from large pyramidal cells travel downward through corticospinal tracts that lead out to peripheral muscles. These impulses from the motor cortex are called action potentials, and each impulse is associated with a single motor neuron. The principle structure of a motor neuron is shown in Fig. 6.IS. The action potential initiates in the cell body, or soma, and travels down a long efferent trunk, called the axon, at a rate of about 80 to 120 m/s. The action potential waveform is the result of a voltage depolarization-repolarization phenomenon across the neuron cell membrane. The membrane ionic potential at rest is distuibed by a surrounding stimulus, and Na ions are allowed to momentarily rush inside. An active transport mechanism, called the Na —K+ pump, quickly returns the transmembrane potential to rest This sequence of events, which lasts about 1 ms, stimulates a succession of nerve impulses or waves that eventually reach muscle... 

Luo C, Rudy Y (1991) A model of the ventricular action potential depolarization, repolarization,... 

The depolarization-repolarization cycle consists of the following phases. 

Six helpful appendices are included Quick guide to cardiac arrhythmias summarizes the details of 20 arrhythmias Cardiac drug overview covers commonly used cardiac drugs Best monitoring leads shows the most beneficial leads to monitor for the most challenging arrhythmias Depolarization-repolarization cycle explains the five phases of this cardiac cycle Action potential curves reviews the cellular changes that occur during the depolarization-repolarization cycle and Cardiac conduction system reviews how electrical impulses affect heart function. 

The Cardiac Cycle. The heart (Eig. lb) performs its function as a pump as a result of a rhythmical spread of a wave of excitation (depolarization) that excites the atrial and ventricular muscle masses to contract sequentially. Maximum pump efficiency occurs when the atrial or ventricular muscle masses contract synchronously (see Eig. 1). The wave of excitation begins with the generation of electrical impulses within the SA node and spreads through the atria. The SA node is referred to as the pacemaker of the heart and exhibits automaticity, ie, it depolarizes and repolarizes spontaneously. The wave then excites sequentially the AV node the bundle of His, ie, the penetrating portion of the AV node the bundle branches, ie, the branching portions of the AV node the terminal Purkinje fibers and finally the ventricular myocardium. After the wave of excitation depolarizes these various stmetures of the heart, repolarization occurs so that each of the stmetures is ready for the next wave of excitation. Until repolarization occurs the stmetures are said to be refractory to excitation. During repolarization of the atria and ventricles, the muscles relax, allowing the chambers of the heart to fill with blood that is to be expelled with the next wave of excitation and resultant contraction. This process repeats itself 60—100 times or beats per minute... 

Glass lA Antiarrhythmic Agents. Class lA antiarrhythmic agents decrease automaticity, ie, depress pacemaker rates, especially ectopic foci rates produce moderate depression of phase 0 depolarization and thus slow conduction in atria, A-V node, His-Purkinje system, and ventricles prolong repolarization, ie, lengthen action potential duration increase refractoriness and depress excitabiHty. These electrophysiological effects are manifested in the ECG by increases in the PR, QRS, and QT intervals. 

Fleca.inide, Elecainide acetate, a fluorobenzamide, is a derivative of procainamide, and has been reported to be efficacious in suppressing both supraventricular and ventricular arrhythmias (26—29). The dmg is generally reserved for patients with serious and life-threatening ventricular arrhythmias. Elecainide depresses phase 0 depolarization of the action potential, slows conduction throughout the heart, and significantly prolongs repolarization (30). The latter effect indicates flecainide may possess some Class III antiarrhythmic-type properties (31). 

A cell may produce early afterdepolarizations that are depolarization during incomplete repolarization. This is possible if the action potential is considerably prolonged. This is the typical mechanism for elicitation of Torsade de Pointes arrhythmia, a typical complication of class III antiarrhythmics and many other drugs. 

Inward Rectifier K+ Channels. Figure 1 The role of inward rectifier (Kir) channels in cardiac action potentials. Depolarization is generated and maintained by Na and Ca currents (/Na, /Ca). Voltage-gated K currents (Kv) and Kir channels contribute to repolarization and maintenance of a negative resting potential. 

Repolarization is a return of membrane potential to its resting value. It refers mostly to repolarization of an action potential, although a more general meaning of returning a membrane potential back to a more negative value after (forced) depolarization is also common. 

In cerebellar Purkinje cells, a TTX-sensitive inward current is elicited, when the membrane was partially repolarized after strong depolarization. This resurgent current contributes to high-frequency repetitive firing of Purkinje neurons. The resurgent current results from open channel block by the cytoplasmic tail of the (34 subunit. The med Nav 1.6 mutant mice show defective synaptic transmission in the neuromuscular junction and degeneration of cerebellar Purkinje cells. 

Other neuronal Cl -channels are Ca " -controlled. Increases in cytosolic Ca enhances the probability of these channels being open [26,27]. These channels stabilize the membrane voltage by clamping it towards the Cl -equilibrium potential. Such channels have been found, e.g., in cultured mouse spinal neurones and in molluscan neurones. They subserve the repolarization phenomena and hence assist Ca -activated -channels. Their conductance is in the small to intermediate range. They are usually gated by depolarization. 

Several intervals and durations are routinely measured on the ECG. The PR interval represents the time of conduction of impulses from the atria to the ventricles through the AV node the normal PR interval in adults is 0.12 to 0.2 seconds. The QRS duration represents the time required for ventricular depolarization, which is normally 0.08 to 0.12 seconds in adults. The QT interval represents the time required for ventricular repolarization. The QT interval varies with heart rate—the faster the heart rate, the shorter the QT interval, and vice versa. Therefore, the QT interval is corrected for heart rate using Bazett s equation3, which is ... 

After an electrical impulse is initiated and conducted, there is a period of time during which cells and fibers cannot be depolarized again. This period of time is referred to as the absolute refractory period (Fig. 6-2),2 and corresponds to phases 1,2, and approximately half of phase 3 repolarization on the action potential. The absolute refractory period also corresponds to the period from the Q wave to approximately the first half of the T wave on the ECG (Fig. 6-2). During this period, if there is a premature stimulus for an electrical impulse, this impulse cannot be conducted, because the tissue is absolutely refractory. 

Salicylic acid depolarized PD In epidermal cells of oat roots also. At pH 4.5, 500 pM salicylic acid caused a transient hyperpolarization followed by a dramatic depolarization to about -45 mV (Figure 2). Removal of salicylic acid produced a transient, partial repolarization. At pH 6.5, salicylic acid did not affect PD. These results with different pH s are consistent with the Influence of salicylic acid on K+ absorption in oat roots (32). 

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