Repolarization current

Cardiac APD is controlled by a fine balance between inward and outward currents in the repolarization phase. Since outward K+ currents, especially the delayed rectifier repolarizing current, IK (which is the sum of two kinetically and pharmacologically distinct types of K+ currents a rapid, 1k and a slow, IKs, component), play an important role during repolarization and in determining the configuration of the action potential, small changes in conductance can significantly alter the effective refractory period, hence the action potential duration. 

Other repolarizing current and drug interactions with different hERG R+ channel subunits have to be characterized... 

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)...

In vitro Disaggregated cells Repolarizing currents (e.g., IKs, IK1, Ito), depolarizing currents (e.g., INa) currents, ICa (whole cell patch-clamp) Disaggregated cells ventricular myocytes mouse atrial tumor cells (AT-1) immortalized cardiac muscle cells (HL-1) Jost et al.,-65 Liu and Antzelevitch 66 Jurkiewicz and Sanguinetti 67 Li et al. 68 Yang and Roden 69 Banyasz et al. 70 Xia et al.71... 

Anderson, M.E., Al-Khatib, S.M., Roden, D.M., and Califf, R.M., Cardiac repolarization current knowledge, criticl gaps and new approaches to drug development and patient management, Am. Heart., 144, 769-781, 2002. 

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)-... 

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

Exceptions are (a) instantaneous activation of the fast depolarizing current and (b) direct coupling of the slow repolarizing current to the slow depolarizing current according to ... 

In the SA node, each normal cardiac impulse is initiated by the spontaneous depolarization of the pacemaker cells (see Chapter 34). When a threshold is reached, an action potential is initiated and conducted through the atrial muscle fibers to the AV node and thence through the Purkinje system to the ventricular muscle. ACh slows the heart rate by decreasing the rate of spontaneous diastolic depolarization (the pacemaker current) and by increasing the repolarizing current at the SA node (a direct effect of fiy subunits of G/G, ) in sum, the membrane potential is more negative and attainment of the threshold potential and the succeeding events in the cardiac cycle are delayed. 

One example of a cell-based assay that has been successfully incorporated into the safety assessment pathway is the assessment of drug-induced proarrhythmia risk based on block of the cardiac repolarization current IKr and the clinical assessment of the electrocardiographic QT interval, as discussed in the ICH S7B and ICH E14 harmonized... 

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... 

Compound 43 (F pre 10) exhibited a nematic phase over a range of 120 °C, and its FE switching has been demonstrated by combining repolarization current measurements, electro-optical characterizations, XRD, and computer simulations. It was concluded that the response is due to field-induced reorganization of polar cybotactic groups within the nematic phase. 

This material is of great potential in the search for the elusive biaxial and FE nematic phases. FE-like switching response is strongly supported by the comparative repolarization current measurements in the nematic and isotropic phases once definitely confirmed by complementary techniques,... 

Indeed, upon cooling from the isotropic through the smectic A phase, a metastable polar phase forms at temperature 82°C, which existed down to the room temperature before the next heating cycle. The phase manifests all polar properties, namely, pyroelectric and piezoelectric effects, repolarization current and optical... 

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... 

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