Repolarizing current, potassium

III Amiodarone Bretylium Sotalol Prolong ventricular action potential, prolong refractoriness, inhibit potassium repolarization currents. Prolong QTc interval. Potential for proarrhythmia (torsades de pointes tachyarrhythmia). 

Outward repolarizing currents oppose the effect of the inward Ica on the plateau phase. This current is carried predominantly through delayed rectifier potassium channels (Ik).These channels are voltage sensitive, with slow inactivation kinetics. Three distinct subpopulations of Ik with differing activation and inactivation kinetics have been described. A rapidly activating subset (Ikf), a slowly inactivating subset (Iks), and an ul-tra-rapidly activating subset to date are identified only in atrial tissue (Ikui)-... 

The excitable membrane of nerve axons, like the membrane of cardiac muscle (see Chapter 14) and neuronal cell bodies (see Chapter 21), maintains a resting transmembrane potential of -90 to -60 mV. During excitation, the sodium channels open, and a fast inward sodium current quickly depolarizes the membrane toward the sodium equilibrium potential (+40 mV). As a result of this depolarization process, the sodium channels close (inactivate) and potassium channels open. The outward flow of potassium repolarizes the membrane toward the potassium equilibrium potential (about -95 mV) repolarization returns the sodium channels to the rested state with a characteristic recovery time that determines the refractory period. The transmembrane ionic gradients are maintained by the sodium pump. These ionic fluxes are similar to, but simpler than, those in heart muscle, and local anesthetics have similar effects in both tissues. 

IKR = Delayed potassium rectifier current QT interval = Repolarization... 

The KCNQl and KCNH2 genes code for two major cardiac repolarizing currents, and mutations in these channels have been shown to cause long QT syndrome (LQTS) type 1 and type 2, respectively (Modell and Lehmann, 2006). iPSC-CMs carrying mutations in these cardiac potassium channels... 

The letter I in the field of cardiac electrophysiology derives from the use of this letter in physics to represent a current the names of multiple ionic currents therefore commence with this letter. The subscript upper case letter K (the chemical symbol for potassium) represents that 4, is a potassium ionic current, and the use of the subscript lower case letter r represents that it is the rapid component of the repolarizing current, one of several potassium currents that each flow through one of several potassium channels. Various types of potassium ionic currents are discussed in more detail in Chap. 9 here, we simply focus on and the ion channel through which it flows. 

It was also apparent that these occurrences were concentration related and almost exclusively linked to delayed cardiac repolarization due to drug-induced inhibition of the rapid delayed-rectifler potassium current (7ki), the main repolarizing current... 

For the most part the selective Class III agents appear to act by inhibition of one or more repolarizing potassiuim currents, especially the delayed rectifier (/k) and/or the inward rectifier (/ki). Less selective agents generally affect sodium currents, as well as potassium currents, which translates to Class I (conduction-slowing) activity. Additional work still needs to be done to increase our understanding of the currents and channels involved in regulation of APD. Care must be taken to evaluate species differences, tissue dif-... 

The actions of sotalol on the delayed rectifier potassium current prolong the ERP in His-Purkinje tissue. As with other members of class III, the electrophysiological action of sotalol is characterized by prolongation of repolarization and an increase in the ERP of ventricular muscle. 

Dofetilide s mechanism of action involves blockade of the cardiac ion channel that carries the rapid component of the delayed rectifier potassium current, IKr. Dofetilide inhibits IKr with no significant effects on other repolarizing potassium currents (e.g., IKs, IKl) over a wide range of concentrations. At plasma concentrations within the therapeutic range, dofetilide has no effect on sodium channels or on either i- or p-adreno-ceptors. 

Mechanism of Action A selective potassium channel blocker that prolongs repolar-ization without affecting conduction velocity by blocking one or more time-dependent potassium currents. Dofetilide has no effect on sodium channels or adrenergic alpha or beta receptors. Therapeutic Effect Terminates reentrant tachyarrhythmias,... 

Schematic diagram of the ion permeability changes and transport processes that occur during an action potential and the diastolic period following it. Yellow indicates inward (depolarizing) membrane currents blue indicates outward (repolarizing) membrane currents. Multiple subtypes of potassium and calcium currents, with different sensitivities to blocking drugs, have been identified. The right side of the figure lists the genes and proteins responsible for each type of channel or transporter.

Most calcium channels become activated and inactivated in what appears to be the same way as sodium channels, but in the case of the most common type of cardiac calcium channel (the "L" type), the transitions occur more slowly and at more positive potentials. The action potential plateau (phases 1 and 2) reflects the turning off of most of the sodium current, the waxing and waning of calcium current, and the slow development of a repolarizing potassium current. 

Ibutilide slows cardiac repolarization by blockade of the rapid component (I ) of the delayed rectifier potassium current. Activation of... 

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