delayed rectifier potassium channels

Summary

Summary: A group of slow opening and closing voltage-gated potassium channels. Because of their delayed activation kinetics they play an important role in controlling ACTION POTENTIAL duration.

Top Publications

  1. Murakoshi H, Shi G, Scannevin R, Trimmer J. Phosphorylation of the Kv2.1 K+ channel alters voltage-dependent activation. Mol Pharmacol. 1997;52:821-8 pubmed
    ..1 can be modulated by direct phosphorylation of the channel protein; such modulation of Kv2.1 could dynamically regulate dendritic excitability. ..
  2. Klemic K, Shieh C, Kirsch G, Jones S. Inactivation of Kv2.1 potassium channels. Biophys J. 1998;74:1779-89 pubmed
    ..quot; These results can be explained by an allosteric model, in which inactivation is favored by activation of voltage sensors, but the open state of the channel is resistant to inactivation. ..
  3. Salataa J, Selnickb H, Lynch J. Pharmacological modulation of I(Ks): potential for antiarrhythmic therapy. Curr Med Chem. 2004;11:29-44 pubmed
    ..It remains to be determined if these properties can be exploited clinically to provide more effective and safer treatment of cardiac arrhythmias. ..
  4. Frolov R, Berim I, Singh S. Inhibition of delayed rectifier potassium channels and induction of arrhythmia: a novel effect of celecoxib and the mechanism underlying it. J Biol Chem. 2008;283:1518-24 pubmed
    ..These observations reveal an unanticipated effect of celecoxib on Drosophila hearts and on heart cells from rats, implicating the inhibition of Kv2 channels as the mechanism underlying this effect. ..
  5. Guan D, Lee J, Tkatch T, Surmeier D, Armstrong W, Foehring R. Expression and biophysical properties of Kv1 channels in supragranular neocortical pyramidal neurones. J Physiol. 2006;571:371-89 pubmed
    ..Kv1 channels should also be important at voltages near threshold and corresponding to interspike intervals. ..
  6. Tsuji Y, Zicha S, Qi X, Kodama I, Nattel S. Potassium channel subunit remodeling in rabbits exposed to long-term bradycardia or tachycardia: discrete arrhythmogenic consequences related to differential delayed-rectifier changes. Circulation. 2006;113:345-55 pubmed
    ..These results point to a crucial role for delayed-rectifier subunit remodeling in TdP susceptibility associated with rate-related cardiac remodeling. ..
  7. Witchel H, Hancox J. Familial and acquired long qt syndrome and the cardiac rapid delayed rectifier potassium current. Clin Exp Pharmacol Physiol. 2000;27:753-66 pubmed
    ..Until such time, awareness of the QT-prolongation risk of particular agents is important for the clinician. ..
  8. Zankov D, Omatsu Kanbe M, Isono T, Toyoda F, Ding W, Matsuura H, et al. Angiotensin II potentiates the slow component of delayed rectifier K+ current via the AT1 receptor in guinea pig atrial myocytes. Circulation. 2006;113:1278-86 pubmed
  9. Frech G, VanDongen A, Schuster G, Brown A, Joho R. A novel potassium channel with delayed rectifier properties isolated from rat brain by expression cloning. Nature. 1989;340:642-5 pubmed
    ..The channels show sigmoidal voltage-dependent activation and do not inactivate within 500 ms. Structurally, drk1 encodes an amino-acid sequence which is more closely related to the Drosophila Shab gene than to the Shaker gene. ..

More Information

Publications62

  1. Andalib P, Wood M, Korn S. Control of outer vestibule dynamics and current magnitude in the Kv2.1 potassium channel. J Gen Physiol. 2002;120:739-55 pubmed
    ..Moreover, the insensitivity of Kv2.1 current magnitude to changes in K+ driving force promotes a more uniform modulation of current over a wide range of membrane potentials by the K+-dependent regulation of outer vestibule conformation...
  2. Lan M, Shi Y, Han Z, Hao Z, Pan Y, Liu N, et al. Expression of delayed rectifier potassium channels and their possible roles in proliferation of human gastric cancer cells. Cancer Biol Ther. 2005;4:1342-7 pubmed
    ..Kv1.5 may be involved in tumor cells proliferation by controlling Ca(2+) entry, and the interference of K(D) channels expression and/or activity could provide a novel strategy to reverse the malignant phenotype of gastric cancer cells. ..
  3. Ji J, Tsuk S, Salapatek A, Huang X, Chikvashvili D, Pasyk E, et al. The 25-kDa synaptosome-associated protein (SNAP-25) binds and inhibits delayed rectifier potassium channels in secretory cells. J Biol Chem. 2002;277:20195-204 pubmed
    ..Taken together we have concluded that SNAP-25 mediates secretion not only through its participation in the exocytotic SNARE complex but also by regulating membrane potential and calcium entry through its interaction with K(DR) channels. ..
  4. Milberg P, Fleischer D, Stypmann J, Osada N, Mönnig G, Engelen M, et al. Reduced repolarization reserve due to anthracycline therapy facilitates torsade de pointes induced by IKr blockers. Basic Res Cardiol. 2007;102:42-51 pubmed
    ..Thus, anthracycline therapy reduces repolarization reserve and thereby represents a novel contributing factor for the development of life-threatening proarrhythmia. ..
  5. Li Smerin Y, Hackos D, Swartz K. alpha-helical structural elements within the voltage-sensing domains of a K(+) channel. J Gen Physiol. 2000;115:33-50 pubmed
    ..In contrast, the distribution of perturbations for S3 and S4 were more complex, suggesting that the latter two helices make more extensive protein contacts, possibly interfacing directly with the shell of the pore domain. ..
  6. Immke D, Wood M, Kiss L, Korn S. Potassium-dependent changes in the conformation of the Kv2.1 potassium channel pore. J Gen Physiol. 1999;113:819-36 pubmed
    ..1 was influenced by the conformational rearrangements, either internal to the selectivity filter or near the outer edge of the external vestibule, that were associated with differences in TEA potency. ..
  7. Heath B, Terrar D. Protein kinase C enhances the rapidly activating delayed rectifier potassium current, IKr, through a reduction in C-type inactivation in guinea-pig ventricular myocytes. J Physiol. 2000;522 Pt 3:391-402 pubmed
    ..IKr seems to be enhanced through a reduction in the C-type inactivation which underlies the rectification of the channel and such a mechanism may occur in other channels with this type of inactivation. ..
  8. Frazier C, George E, Jones S. Apparent change in ion selectivity caused by changes in intracellular K(+) during whole-cell recording. Biophys J. 2000;78:1872-80 pubmed
    ..Long steps to V(R) caused inactivation, but no change in V(R). We conclude that current-dependent changes in [K(+)](i) need to be carefully evaluated when studying large K(+) currents in small cells. ..
  9. Varro A, Biliczki P, Iost N, Virag L, Hála O, Kovacs P, et al. Theoretical possibilities for the development of novel antiarrhythmic drugs. Curr Med Chem. 2004;11:1-11 pubmed
    ..Further research is needed to develop specific K-channel blockers, such as I(Kur)and I(KAch) inhibitors, and to establish their possible therapeutic value. ..
  10. Michel S, Manivannan K, Zaritsky J, Block G. A delayed rectifier current is modulated by the circadian pacemaker in Bulla. J Biol Rhythms. 1999;14:141-50 pubmed
    ..However, the IA and IK(Ca) currents were not affected by the circadian pacemaker. ..
  11. Brette F, Machado B, Cros C, Incardona J, Scholz N, Block B. Crude oil impairs cardiac excitation-contraction coupling in fish. Science. 2014;343:772-6 pubmed publisher
    ..Our findings demonstrate a cardiotoxic mechanism by which crude oil affects the regulation of cellular excitability, with implications for life-threatening arrhythmias in vertebrates. ..
  12. Ducroq J, Moha Ou Maati H, Guilbot S, Dilly S, Laemmel E, Pons Himbert C, et al. Dexrazoxane protects the heart from acute doxorubicin-induced QT prolongation: a key role for I(Ks). Br J Pharmacol. 2010;159:93-101 pubmed publisher
    ..This effect was prevented by dexrazoxane. This result is important because it illustrates the danger of neglecting I(Ks) in favour of hERG screening alone, for early preclinical testing for possible induction of torsade de pointes. ..
  13. Rohra D, Saito S, Ohizumi Y. Strain-specific effects of acidic pH on contractile state of aortas from Wistar and Wistar Kyoto rats. Eur J Pharmacol. 2003;476:123-30 pubmed
    ..The sustained and transient relaxant responses to acidic pH in Wistar and WKY aortas, respectively, are due to decrease in [Ca2+]i levels, but this decrease in [Ca2+]i is independent of the activation of K+ channels. ..
  14. Bosch R, Schneck A, Csillag S, Eigenberger B, Gerlach U, Brendel J, et al. Effects of the chromanol HMR 1556 on potassium currents in atrial myocytes. Naunyn Schmiedebergs Arch Pharmacol. 2003;367:281-8 pubmed
    ..Given the potential advantages of I(Ks) vs. I(Kr) blockade, the drug's new mechanism of action warrants further investigation to clarify its role as an antiarrhythmic agent. ..
  15. Cornfield D, Saqueton C, Porter V, Herron J, Resnik E, Haddad I, et al. Voltage-gated K(+)-channel activity in ovine pulmonary vasculature is developmentally regulated. Am J Physiol Lung Cell Mol Physiol. 2000;278:L1297-304 pubmed
    ..We conclude that there are maturation-dependent changes in PASMC O(2) sensing that may render the adult PASMCs more responsive to acute hypoxia...
  16. Lu Y, Hanna S, Tang G, Wang R. Contributions of Kv1.2, Kv1.5 and Kv2.1 subunits to the native delayed rectifier K(+) current in rat mesenteric artery smooth muscle cells. Life Sci. 2002;71:1465-73 pubmed
    ..A control antibody (anti-GIRK1) also had no effect on the native Kv currents. This study demonstrates that Kv1.2, Kv1.5, and Kv2.1 subunit genes all contribute to the formation of the native Kv channels in rat mesenteric artery SMCs. ..
  17. Gonzalez T, Longobardo M, Caballero R, Delpón E, Tamargo J, Valenzuela C. Effects of bupivacaine and a novel local anesthetic, IQB-9302, on human cardiac K+ channels. J Pharmacol Exp Ther. 2001;296:573-83 pubmed
    ..5, Kv2.1, Kv4.3, and HERG channels; and 2) small differences at the N-substituent of these drugs do not affect the drug-induced block of Kv2.1, Kv4.3, or HERG, but specifically modify block of hKv1.5 channels. ..
  18. Kerschensteiner D, Soto F, Stocker M. Fluorescence measurements reveal stoichiometry of K+ channels formed by modulatory and delayed rectifier alpha-subunits. Proc Natl Acad Sci U S A. 2005;102:6160-5 pubmed
    ..1 subunits and one Kv9.3 subunit. Strikingly, despite this uneven stoichiometry, we find that heteromeric Kv2.1/Kv9.3 channels maintain a pseudosymmetric arrangement of subunits around the central pore. ..
  19. Deng P, Pang Z, Zhang Y, Xu Z. Increase of delayed rectifier potassium currents in large aspiny neurons in the neostriatum following transient forebrain ischemia. Neuroscience. 2005;131:135-46 pubmed
    ..The increase of Ik in LA neurons might be one of the protective mechanisms against ischemic insult. ..
  20. Plane F, Johnson R, Kerr P, Wiehler W, Thorneloe K, Ishii K, et al. Heteromultimeric Kv1 channels contribute to myogenic control of arterial diameter. Circ Res. 2005;96:216-24 pubmed
    ..It is concluded that K(DR) channels composed of heteromultimers of Kv1 subunits play a critical role in myogenic control of arterial diameter. ..
  21. Liu H, Lin J. A set of homology models of pore loop domain of six eukaryotic voltage-gated potassium channels Kv1.1-Kv1.6. Proteins. 2004;55:558-67 pubmed
    ..The homology models of these Kv channels provide particularly attractive subjects for further structure-based studies. ..
  22. Stoffel R, Randall R, Premont R, Lefkowitz R, Inglese J. Palmitoylation of G protein-coupled receptor kinase, GRK6. Lipid modification diversity in the GRK family. J Biol Chem. 1994;269:27791-4 pubmed
    ..This lipid modification provides a structural basis for potential regulation of the subcellular distribution of GRK6 through acylation/deacylation cycles. ..
  23. Tan H, Sun L, Wang X, Ye T. Effect of etomidate on voltage-dependent potassium currents in rat isolated hippocampal pyramidal neurons. Chin Med J (Engl). 2010;123:702-6 pubmed
    ..Etomidate potently inhibited I(K(DR)) but not I(K(A)) in rat hippocampal pyramidal neurons. I(K(DR)) was inhibited by etomidate in a concentration-dependent manner, while I(K(A)) remained unaffected. ..
  24. Rutherford M, Roberts W. Spikes and membrane potential oscillations in hair cells generate periodic afferent activity in the frog sacculus. J Neurosci. 2009;29:10025-37 pubmed publisher
    ..These results show that some frog saccular hair cells can generate spontaneous rhythmic activity that may drive periodic background activity in afferent axons. ..
  25. Tsujimae K, Murakami S, Kurachi Y. In silico study on the effects of IKur block kinetics on prolongation of human action potential after atrial fibrillation-induced electrical remodeling. Am J Physiol Heart Circ Physiol. 2008;294:H793-800 pubmed
    ..This modeling study suggests that a simple voltage-clamp protocol with a short pulse of approximately 10 ms at 1 Hz may be useful to identify the effective anti-AF drugs among various I(Kur) blockers. ..
  26. Bentley G, Brooks M, O Neill C, Findlay J. Determinants of potassium channel assembly localised within the cytoplasmic C-terminal domain of Kv2.1. Biochim Biophys Acta. 1999;1418:176-84 pubmed
    ..These data demonstrate that C-terminal interactions are important for driving Kv2.1 channel assembly and that distinct regions of the C-terminal domain may have differential effects on the formation of functional tetramers. ..
  27. Belevych A, Beck R, Tammaro P, Poston L, Smirnov S. Developmental changes in the functional characteristics and expression of voltage-gated K+ channel currents in rat aortic myocytes. Cardiovasc Res. 2002;54:152-61 pubmed
    ..These changes could play an important role in adaptation to extrauterine life. ..
  28. Chen Y, Lin C, Lin P, Tsai M. Cocaine elicits action potential bursts in a central snail neuron: the role of delayed rectifying K+ current. Neuroscience. 2006;138:257-80 pubmed
    ..It is concluded that cocaine elicits action potential bursts in the central snail RP4 neuron and that the effect is closely related to the inhibitory effects on the delayed rectifying K(+) current. ..
  29. Zhang W, Jin H, Wang X. Effects of presenilins and beta-amyloid precursor protein on delayed rectifier potassium channels in cultured rat hippocampal neurons. Acta Pharmacol Sin. 2004;25:181-5 pubmed
    ..effects of presenilin-1 (PS-1), presenilin-2 (PS-2), and amyloid beta-protein precursor (APP695) on delayed rectifier potassium channels (IK) in the cultured rat hippocampal neurons...
  30. Hasan S, Redzic Z, Alshuaib W. Hydrogen peroxide-induced reduction of delayed rectifier potassium current in hippocampal neurons involves oxidation of sulfhydryl groups. Brain Res. 2013;1520:61-9 pubmed publisher
  31. Lee S, Kim Y, Kim K, Choe H, Jo S. Blockade of HERG human K+ channels and IKr of guinea-pig cardiomyocytes by the antipsychotic drug clozapine. Br J Pharmacol. 2006;148:499-509 pubmed
    ..Our findings collectively suggest that blockade of HERG currents and I(Kr), but not I(Ks), may contribute to the arrhythmogenic side effects of clozapine. ..
  32. Nerbonne J, Nichols C, Schwarz T, Escande D. Genetic manipulation of cardiac K(+) channel function in mice: what have we learned, and where do we go from here?. Circ Res. 2001;89:944-56 pubmed
  33. Qin Y, Qi J, Qiao J. Apolipoprotein E4 suppresses delayed-rectifier potassium channels in membrane patches excised from hippocampal neurons. Synapse. 2006;59:82-91 pubmed
    ..We propose that the overproduction of apoE4 in neurons may suppress normal IK channel activities and thus be responsible for the late-developed neuronal damages related to the pathogenesis of AD. ..
  34. Knollmann B, Casimiro M, Katchman A, Sirenko S, Schober T, Rong Q, et al. Isoproterenol exacerbates a long QT phenotype in Kcnq1-deficient neonatal mice: possible roles for human-like Kcnq1 isoform 1 and slow delayed rectifier K+ current. J Pharmacol Exp Ther. 2004;310:311-8 pubmed
    ..This idea is further supported by new RNA data showing that there is a high degree of homology (>88% amino acid identity) between the predominant human and mouse cardiac Kcnq1 isoforms. ..
  35. Soliven B, Ma L, Bae H, Attali B, Sobko A, Iwase T. PDGF upregulates delayed rectifier via Src family kinases and sphingosine kinase in oligodendroglial progenitors. Am J Physiol Cell Physiol. 2003;284:C85-93 pubmed
  36. Shimizu K, Shintani Y, Ding W, Matsuura H, Bamba T. Potentiation of slow component of delayed rectifier K(+) current by cGMP via two distinct mechanisms: inhibition of phosphodiesterase 3 and activation of protein kinase G. Br J Pharmacol. 2002;137:127-37 pubmed
    ..5. These results strongly suggest that intracellular cGMP potentiates I(Ks) not only by blocking PDE3 but also by activating PKG in guinea-pig SA node cells. ..
  37. Tian Y, Liu Z, Yao Y, Yang Z, Zhang T. Effect of alpha-cypermethrin and theta-cypermethrin on delayed rectifier potassium currents in rat hippocampal neurons. Neurotoxicology. 2009;30:269-73 pubmed
    ..Cypermethrin-altered properties of voltage gated delayed rectifier K+ channels may contribute to neurotoxicity by eliciting abnormal electrical discharges in hippocampal CA3 neurons. ..
  38. Eghbali M, Olcese R, Zarei M, Toro L, Stefani E. External pore collapse as an inactivation mechanism for Kv4.3 K+ channels. J Membr Biol. 2002;188:73-86 pubmed
  39. Grammatopoulos T, Johnson V, Moore S, Andres R, Weyhenmeyer J. Angiotensin type 2 receptor neuroprotection against chemical hypoxia is dependent on the delayed rectifier K+ channel, Na+/Ca2+ exchanger and Na+/K+ ATPase in primary cortical cultures. Neurosci Res. 2004;50:299-306 pubmed
    ..These findings further suggest that the mechanism of AT(2) receptor mediated neuroprotection is coupled to activation of the delayed rectifier K(+) channel, NCX and ATPase. ..
  40. Hassinen M, Laulaja S, Paajanen V, Haverinen J, Vornanen M. Thermal adaptation of the crucian carp (Carassius carassius) cardiac delayed rectifier current, IKs, by homomeric assembly of Kv7.1 subunits without MinK. Am J Physiol Regul Integr Comp Physiol. 2011;301:R255-65 pubmed publisher
    ..We suggest that the homomeric K(v)7.1 channel assembly is an evolutionary thermal adaptation of ectothermic hearts and the heteromeric K(v)7.1/MinK channels evolved later to adapt I(Ks) to high body temperature of endotherms. ..
  41. Zhao M, Zhang W, Zhao C. [The effects of Sphing-1-phosphate(S1P) on the potassium channel of the ventricular myocytes]. Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2009;25:56-9 pubmed
    ..05, n = 6). S1P inhibits delayed rectifier potassium current of ventricular myocyte in guinea pig remarkably, S1P shows no effects on delayed rectifier potassium current of ventricular myocyte in guinea pig. ..
  42. Garrido J, Giraud P, Carlier E, Fernandes F, Moussif A, Fache M, et al. A targeting motif involved in sodium channel clustering at the axonal initial segment. Science. 2003;300:2091-4 pubmed
    ..Thus, this motif may play a fundamental role in controlling electrical excitability during development and plasticity. ..
  43. Takahara A, Sugiyama A, Satoh Y, Wang K, Honsho S, Hashimoto K. Halothane sensitizes the canine heart to pharmacological IKr blockade. Eur J Pharmacol. 2005;507:169-77 pubmed
    ..Thus, the halothane-anesthetized canine model can be useful for predicting the in vivo I(Kr) blocking property of new drugs. ..
  44. Chen B, Peng H, Wu S. Dexmedetomidine, an alpha2-adrenergic agonist, inhibits neuronal delayed-rectifier potassium current and sodium current. Br J Anaesth. 2009;103:244-54 pubmed publisher
    ..Inhibitory effects on I(K(DR)) and I(Na) constitute one of the underlying mechanisms through which DEX and its structurally related compounds might affect neuronal activity in vivo. ..
  45. Gao Z, Chen X, Jiang H, Liu H, Hu G. Electrophysiological characterization of a novel Kv channel blocker N,N'-[oxybis(2,1-ethanediyloxy-2,1-ethanediyl) ]bis(4-methyl)-benzenesulfonamide found in virtual screening. Acta Pharmacol Sin. 2008;29:405-12 pubmed publisher
    ..In addition, the compound differentially moderates the inactivation kinetics of the K+ channels through allosteric mechanisms. ..
  46. Du X, Lau C, Chiu S, Tse H, Gerlach U, Li G. Effects of chromanol 293B on transient outward and ultra-rapid delayed rectifier potassium currents in human atrial myocytes. J Mol Cell Cardiol. 2003;35:293-300 pubmed
    ..The results indicate that 293B significantly inhibits the major repolarization K(+) currents I(to1) and I(Kur) in human atrial myocytes. ..
  47. Stecyk J, Paajanen V, Farrell A, Vornanen M. Effect of temperature and prolonged anoxia exposure on electrophysiological properties of the turtle (Trachemys scripta) heart. Am J Physiol Regul Integr Comp Physiol. 2007;293:R421-37 pubmed
    ..These changes likely prepare cardiac muscle for winter anoxia conditions. ..
  48. Choi S, Parajuli S, Lim G, Kim J, Yeum C, Yoon P, et al. Imipramine inhibits A-type delayed rectifier and ATP-sensitive K+ currents independent of G-protein and protein kinase C in murine proximal colonic myocytes. Arch Pharm Res. 2006;29:998-1005 pubmed
    ..These results suggest that imipramine inhibits A-type delayed rectifier K+ currents and KATP currents in a manner independent of G-protein and protein kinase C. ..
  49. Christ T, Wettwer E, Ravens U. Letter by Christ et al regarding article, "Angiotensin II potentiates the slow component of delayed rectifier K+ current via the AT1 receptor in guinea pig atrial myocytes". Circulation. 2006;114:e565; author reply e566 pubmed
  50. Sakatani T, Shirayama T, Yamamoto T, Mani H, Shiraishi H, Matsubara H. Cardiac hypertrophy diminished the effects of isoproterenol on delayed rectifier potassium current in rat heart. J Physiol Sci. 2006;56:173-81 pubmed
    ..2 +/- 0.05%), as much as in sham-operated rats. We concluded that in hypertrophic hearts, I(K) was not increased by isoproterenol because of the enhanced activity of phosphodiesterase, which leads to excessive APD prolongation. ..
  51. Chen X, Johnston D. Voltage-gated ion channels in dendrites of hippocampal pyramidal neurons. Pflugers Arch. 2006;453:397-401 pubmed
    ..In this report, we provide some new evidence for the role of the delayed-rectifier K(+) channel in shaping the dendritic action potential at different membrane potentials. ..
  52. Fedida D, Chen F, Zhang X. The 1997 Stevenson Award Lecture. Cardiac K+ channel gating: cloned delayed rectifier mechanisms and drug modulation. Can J Physiol Pharmacol. 1998;76:77-89 pubmed
    ..In this way we can uncover the detailed mechanisms of action of K+ channel blockers such as tetraethylammonium ions and 4-aminopyridine, and antiarrhythmic agents such as nifedipine and quinidine. ..
  53. Cornfield D, Resnik E, Herron J, Abman S. Chronic intrauterine pulmonary hypertension decreases calcium-sensitive potassium channel mRNA expression. Am J Physiol Lung Cell Mol Physiol. 2000;279:L857-62 pubmed
    ..We conclude that lung K(Ca) channel mRNA expression is decreased in an ovine model of PPHN. Decreased K(Ca) channel gene expression may contribute to the abnormal pulmonary vascular reactivity associated with PPHN...