Effects of IKur blocker MK-0448 on human right atrial action potentials from patients in sinus rhythm and in permanent atrial fibrillation

Frontiers in Pharmacology

Volumn 5 MAR, Issue , 2014, Pages

  Loose, Simone ^a   Mueller, Judith ^a   Wettwer, Erich ^a   Knaut, Michael ^b   Ford, John ^c   Milnes, James ^c   Ravens, Ursula ^a  

^a DRESDEN UNIVERSITY OF TECHNOLOGY   (Germany)

^b University Heart Center Dresden   (Germany)

^c Xention Limited   (United Kingdom)

Author keywords

Atrial fibrillation; Human right atrial action potentials; Kv1.5; MK 0448

Indexed keywords

ANGIOTENSIN 1 RECEPTOR ANTAGONIST; ANTIARRHYTHMIC AGENT; ANTILIPEMIC AGENT; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; CALCIUM CHANNEL BLOCKING AGENT; DIGITALIS; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; DIURETIC AGENT; MK 0448; NITRATE; POTASSIUM CHANNEL BLOCKING AGENT; POTASSIUM CHANNEL KV1.5; UNCLASSIFIED DRUG;

ADULT; AGED; ARTICLE; CLINICAL ARTICLE; CONTROLLED STUDY; CORONARY ARTERY DISEASE; DRUG MECHANISM; FEMALE; HEART ATRIUM FIBRILLATION; HEART ATRIUM REMODELING; HEART MUSCLE FIBER MEMBRANE POTENTIAL; HEART MUSCLE REFRACTORY PERIOD; HEART REPOLARIZATION; HUMAN; MALE; MOUSE; NONHUMAN; SINUS RHYTHM;

EID: 84897943983     PISSN: None     EISSN: 16639812     Source Type: Journal    
DOI: 10.3389/fphar.2014.00026     Document Type: Article

References (23)

1. Amos, G. J., Wettwer, E., Metzger, F., Li, Q., Himmel, H. M., and Ravens, U. (1996). Differences between outward currents of human atrial and subepicardial ventricular myocytes. J. Physiol. 491(Pt 1), 31-50.
2. Attuel, P., Childers, R., Cauchemez, B., Poveda, J., Mugica, J., and Coumel, P. (1982). Failure in the rate adaptation of the atrial refractory period: its relationship to vulnerability. Int. J. Cardiol. 2, 179-197. doi: 10.1016/0167-5273(82)90032-8.
3. Christ, T., Wettwer, E., Voigt, N., Hala, O., Radicke, S., Matschke, K., et al. (2008). Pathology-specific effects of the I(Kur)/I(to)/I(K,ACh) blocker AVE0118 on ion channels in human chronic atrial fibrillation. Br. J. Pharmacol. 154, 1619-1630. doi: 10.1038/bjp.2008.209.
4. Christophersen, I. E., Olesen, M. S., Liang, B., Andersen, M. N., Larsen, A. P., Nielsen, J. B., et al. (2013). Genetic variation in KCNA5: impact on the atrial-specific potassium current IKur in patients with lone atrial fibrillation. Eur. Heart J. 34, 1517-1525. doi: 10.1093/eurheartj/ehs442.
5. Daoud, E. G., Bogun, F., Goyal, R., Harvey, M., Man, K. C., Strickberger, S. A., et al. (1996). Effect of atrial fibrillation on atrial refractoriness in humans. Circulation 94, 1600-1606. doi: 10.1161/01.CIR.94.7.1600.
6. Dobrev, D., and Ravens, U. (2003). Remodeling of cardiomyocyte ion channels in human atrial fibrillation. Basic Res. Cardiol. 98, 137-148. doi: 10.1007/s00395-003-0409-8.
7. Ford, J., Milnes, J., Wettwer, E., Christ, T., Rogers, M., Sutton, K., et al. (2013). Human electrophysiological and pharmacological properties of XEN-D0101: a novel atrial selective Kv1.5/IKur inhibitor. J. Cardiovasc. Pharmacol. 61, 408-415. doi: 10.1097/FJC.0b013e31828780eb.
8. Ford, J. W., and Milnes, J. T. (2008). New drugs targeting the cardiac ultra-rapid delayed-rectifier current (I Kur): rationale, pharmacology and evidence for potential therapeutic value. J. Cardiovasc. Pharmacol. 52, 105-120. doi: 10.1097/FJC.0b013e3181719b0c.
9. Franz, M. R., Karasik, P. L., Li, C., Moubarak, J., and Chavez, M. (1997). Electrical remodeling of the human atrium: similar effects in patients with chronic atrial fibrillation and atrial flutter. J. Am. Coll. Cardiol. 30, 1785-1792. doi: 10.1016/S0735-1097(97)00385-9.
10. Gintant, G. A. (2000). Characterization and functional consequences of delayed rectifier current transient in ventricular repolarization. Am. J. Physiol. Heart Circ. Physiol. 278, H806-H817.
11. Haissaguerre, M., Jais, P., Shah, D. C., Takahashi, A., Hocini, M., Quiniou, G., et al. (1998). Spontaneous initiation of atrial fibrillation by ectopic beats originating in the pulmonary veins. N. Engl. J. Med. 339, 659-666. doi: 10.1056/NEJM199809033391003.
12. Lynch, J. J. Jr., Houle, M. S., Stump, G. L., Wallace, A. A., Gilberto, D. B., Jahansouz, H., et al. (1999). Antiarrhythmic efficacy of selective blockade of the cardiac slowly activating delayed rectifier current, I(Ks), in canine models of malignant ischemic ventricular arrhythmia. Circulation 100, 1917-1922. doi: 10.1161/01.CIR.100.18.1917.
13. + channel protein in explanted cardiac tissue. J. Clin. Invest. 96, 282-292. doi: 10.1172/JCI118032.
14. Olson, T. M., Alekseev, A. E., Liu, X. K., Park, S., Zingman, L. V., Bienengraeber, M., et al. (2006). Kv1.5 channelopathy due to KCNA5 loss-of-function mutation causes human atrial fibrillation. Hum. Mol. Genet. 15, 2185-2191. doi: 10.1093/hmg/ddl143.
15. Pavri, B. B., Greenberg, H. E., Kraft, W. K., Lazarus, N., Lynch, J. J., Salata, J. J., et al. (2012). MK-0448, a specific Kv1.5 inhibitor: safety, pharmacokinetics and pharmacodynamic electrophysiology in experimental animal models and in humans. Circ. Arrhythm. Electrophysiol. 5, 1193-1201. doi: 10.1161/CIRCEP.111.969782.
16. Radicke, S., Cotella, D., Graf, E. M., Banse, U., Jost, N., Varro, A., et al. (2006). Functional modulation of the transient outward current Ito by KCNE beta-subunits and regional distribution in human non-failing and failing hearts. Cardiovasc. Res, 71, 695-703. doi: 10.1016/j.cardiores.2006.06.017.
17. Ravens, U. (2010). Antiarrhythmic therapy in atrial fibrillation. Pharmacol. Ther. 128, 129-145. doi: 10.1016/j.pharmthera.2010.06.004.
18. Ravens, U., and Wettwer, E. (2011). Ultra-rapid delayed rectifier channels: molecular basis and therapeutic implications. Cardiovasc. Res. 89, 776-785. doi: 10.1093/cvr/cvq398.
19. Regan, C. P., Wallace, A. A., Cresswell, H. K., Atkins, C. L., and Lynch, J. J. Jr. (2006). In vivo cardiac electrophysiologic effects of a novel diphenylphosphine oxide IKur blocker, (2-Isopropyl-5-methylcyclohexyl) diphenylphosphine oxide, in rat and nonhuman primate. J. Pharmacol. Exp. Ther. 316, 727-732. doi: 10.1124/jpet.105.094839.
20. Snyders, D. J., Tamkun, M. M., and Bennett, P. B. (1993). A rapidly activating and slowly inactivating potassium channel cloned from human heart. Functional analysis after stable mammalian cell culture expression. J. Gen. Physiol. 101, 513-543. doi: 10.1085/jgp.101.4.513.
21. Tamargo, J., Caballero, R., Gomez, R., and Delpon, E. (2009). I(Kur)/Kv1.5 channel blockers for the treatment of atrial fibrillation. Expert Opin. Investig. Drugs 18, 399-416. doi: 10.1517/13543780902762850.
22. + current similar to Kv1.5 cloned channel currents. Circ. Res. 73, 1061-1076. doi: 10.1161/01.RES.73.6.1061.
23. Wettwer, E., Hala, O., Christ, T., Heubach, J. F., Dobrev, D., Knaut, M., et al. (2004). Role of IKur in controlling action potential shape and contractility in the human atrium: influence of chronic atrial fibrillation. Circulation 110, 2299-2306. doi: 10.1161/01.CIR.0000145155.60288.71.