Delayed-rectifying potassium channel

Cyclo(Trp-Pro) and cyclo(Tyr-Pro) blocked delayed-rectifier potassium channels. 

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)-... 

Bruggemann A, Stiihmer W, Pardo LA (1997) Mitosis-promoting factor-mediated suppression of a cloned delayed rectifier potassium channel expressed in Xenopus oocytes. Proc Natl Acad Sci USA 94 537-542... 

Spruce, A. E., Standen, N. B., and Stanfield, P. R. (1989). Rubidium ions and the gating of delayed rectifier potassium channels of frog skeletal-muscle. J. Physiol. (London) 411, 597-610. 

Fleischmann, B.K., Hay, D.W.P. and Kotlikoff, M.I. (1994). Control of basal tone by delayed rectifier potassium channels in human airways. Am. J. Resp. Crit. Care Med. 149 (4), A1080. 

BRL-32872 is a new anti-arrhythmic drug with balanced class-III and class-IV actions, which blocks the rapid component of the cardiac delayed rectifier potassium channel IK(r) and its molecular correlate... 

Shibasaki T. 1987. Conductance and kinetics of delayed rectifier potassium channels in nodal cells of the rabbit heart. J. Physiol. 387 227-50... 

Sanguinetti MC. 1999. Dysfunction of delayed rectifier potassium channels in an inherited cardiac arrhythmia. Ann. NY Acad. Sci. 868 406-13... 

Poling JS, Karanian JW, Salem N Jr, Vicini S. Time- and voltage-dependent block of delayed rectifier potassium channels by docosahexaenoic acid. Mol Pharmacol 1995 47 381-390. 

Figure 3 The enantiomers of halofantrine have similar antimalarial activities but may differ in their cardiotoxic effects. The figure illustrates the ability of varying concentrations of halofantrine enantiomers to inhibit the delayed rectifier potassium channel in feline ventricular myocytes. The (+) enantiomer appears to be more potent. (Figure plotted from data presented in Table II of Ref 16). 

Prolongation of QT interval may be predicted in vitro by patch clamp electrophysiology in mammalian cells transfected with the human ether-d-go-go-related gene (hERG), a subunit of the (cardiac rapidly activating delayed rectifier potassium channel), or by measuring a compound s abihty... 

Other potassium channels also play important roles here. For example, Kv4.3/ KChIP complex conducts the transient outward current, Ito, responsible for the descending phase 1 of the cardiac action potential, whereas Kvl.5 is underlying the ultra rapid delayed rectifying current, IKur, responsible for descending phase 2. Finally, inward rectifier potassium channel (Kir2 family) is responsible for IKl current, which maintains the action potential close to or at the resting level (phase 4). 

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. 

Dofetilide has class 3 action potential prolonging action. This action is effected by a dose-dependent blockade of the rapid component of the delayed rectifier potassium current, IKr, and the blockade of IKr increases in hypokalemia. Dofetilide produces no relevant blockade of the other potassium channels or the sodium channel. Because of the slow rate of recovery from blockade, the extent of blockade shows little dependence on stimulation frequency. However, dofetilide does show less action potential prolongation at rapid rates because of the increased importance of other potassium channels such as IKs at higher frequencies. 

QT interval prolongation induced by phenothiazines suggests that potassium channels responsible for the repolarization phase of myocardial action potential are naturally the first candidates for the possible interaction with these drugs. Wooltorton and Mathie [244] using a whole-cell voltage clamp found that in isolated rat sympathetic neurons, CPZ (9) inhibited mostly delayed rectified potassium current, leaving the transient K+ current almost... 

This review focuses on the recent discovery and development of chemical entities targeting the Kvl.5 potassium channel subunit for the treatment of atrial arrhythmias. This strategy is based on the expression of the ultrarapidly activating delayed rectifier potassium current, /Run in atria but not ventricles of humans, and on the molecular characterization of the Kvl.5 channel subunit as a structural correlate of JRur [1-6]. Although no perfectly selective Kvl.5... 

Figure 13-3 Potential adverse effects of Hi antihistamines through central nervous system and effect on various receptors and through ion channels. (Igr = rapid component of the delayed rectifier potassium current.) (Adapted with permission from Simons PER.Advances in Hi-antihistamines. N Engl J Med 2004 351 2204.)...

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