| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1 Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, University of Manitoba, Winnipeg, Manitoba R2H 2A6; and 2 Division of Cardiology, Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8
The Na+/Ca2+ exchanger plays a prominent role in regulating intracellular Ca2+ levels in cardiac myocytes and can serve as both a Ca2+ influx and efflux pathway. A novel inhibitor, KB-R7943, has been reported to selectively inhibit the reverse mode (i.e., Ca2+ entry) of Na+/Ca2+ exchange transport, although many aspects of its inhibitory properties remain controversial. We evaluated the inhibitory effects of KB-R7943 on Na+/Ca2+ exchange currents using the giant excised patch-clamp technique. Membrane patches were obtained from Xenopus laevis oocytes expressing the cloned cardiac Na+/Ca2+ exchanger NCX1.1, and outward, inward, and combined inward-outward currents were studied. KB-R7943 preferentially inhibited outward (i.e., reverse) Na+/Ca2+ exchange currents. The inhibitory mechanism consists of direct effects on the transport machinery of the exchanger, with additional influences on ionic regulatory properties. Competitive interactions between KB-R7943 and the transported ions were not observed. The antiarrhythmic effects of KB-R7943 were then evaluated in an ischemia-reperfusion model of cardiac injury in Langendorff-perfused whole rabbit hearts using electrocardiography and measurements of left ventricular pressure. When 3 µM KB-R7943 was applied for 10 min before a 30-min global ischemic period, ventricular arrhythmias (tachycardia and fibrillation) associated with both ischemia and reperfusion were almost completely suppressed. The observed electrophysiological profile of KB-R7943 and its protective effects on ischemia-reperfusion-induced ventricular arrhythmias support the notion of a prominent role of Ca2+ entry via reverse Na+/Ca2+ exchange in this process.
sodium/calcium; NCX1.1; giant excised patch clamp; electrophysiology
This article has been cited by other articles:
|
|
 |
|
  M. K. Klose, G. L. Boulianne, R. M. Robertson, and H. L. Atwood Role of ATP-Dependent Calcium Regulation in Modulation of Drosophila Synaptic Thermotolerance J Neurophysiol, August 1, 2009; 102(2): 901 - 913. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Minami, Y.-f. Xia, and R. S. Zucker Increased Ca2+ influx through Na+/Ca2+ exchanger during long-term facilitation at crayfish neuromuscular junctions J. Physiol., December 1, 2007; 585(2): 413 - 427. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Becker, L. M. Moir, V. A. Snetkov, and P. I. Aaronson Hypoxic pulmonary vasoconstriction in intact rat intrapulmonary arteries is not initiated by inhibition of Na+-Ca2+ exchange Am J Physiol Lung Cell Mol Physiol, October 1, 2007; 293(4): L982 - L990. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. K. Saini and N. S. Dhalla Sarcolemmal cation channels and exchangers modify the increase in intracellular calcium in cardiomyocytes on inhibiting Na+-K+-ATPase Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H169 - H181. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. P. Ander, C. Hurtado, C. S. Raposo, T. G. Maddaford, J. F. Deniset, L. V. Hryshko, G. N. Pierce, and A. Lukas Differential sensitivities of the NCX1.1 and NCX1.3 isoforms of the Na+-Ca2+ exchanger to {alpha}-linolenic acid Cardiovasc Res, January 15, 2007; 73(2): 395 - 403. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Takeuchi, S. Tatsumi, N. Sarai, K. Terashima, S. Matsuoka, and A. Noma Ionic Mechanisms of Cardiac Cell Swelling Induced by Blocking Na+/K+ Pump As Revealed by Experiments and Simulation J. Gen. Physiol., November 1, 2006; 128(5): 495 - 507. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Wongcharoen, Y.-C. Chen, Y.-J. Chen, C.-M. Chang, H.-I Yeh, C.-I Lin, and S.-A. Chen Effects of a Na+/Ca2+ exchanger inhibitor on pulmonary vein electrical activity and ouabain-induced arrhythmogenicity Cardiovasc Res, June 1, 2006; 70(3): 497 - 508. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Iwamoto Vascular Na+/Ca2+ exchanger: implications for the pathogenesis and therapy of salt-dependent hypertension Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2006; 290(3): R536 - R545. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Tan, Z. Ma, L. Han, R. Du, L. Zhao, X. Wei, D. Hou, B. H. Johnstone, M. R. Farlow, and Y. Du Caffeic acid phenethyl ester possesses potent cardioprotective effects in a rabbit model of acute myocardial ischemia-reperfusion injury Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H2265 - H2271. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Bokenes, I. Sjaastad, and O. M. Sejersted Artifactual contractions triggered by field stimulation of cardiomyocytes J Appl Physiol, May 1, 2005; 98(5): 1712 - 1719. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Lee, N. S. Visen, N. S. Dhalla, H. D. Le, M. Isaac, P. Choptiany, G. Gross, A. Omelchenko, T. Matsuda, A. Baba, et al. Inhibitory Profile of SEA0400 [2-[4-[(2,5-Difluorophenyl)methoxy]phenoxy]-5-ethoxyaniline] Assessed on the Cardiac Na+-Ca2+ Exchanger, NCX1.1 J. Pharmacol. Exp. Ther., November 1, 2004; 311(2): 748 - 757. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Weiss, M. Baek, and W. Kang Systems analysis of digoxin kinetics and inotropic response in the rat heart: effects of calcium and KB-R7943 Am J Physiol Heart Circ Physiol, October 1, 2004; 287(4): H1857 - H1867. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Baczko, W. R Giles, and P. E Light Resting Membrane Potential Regulates Na+-Ca2+ Exchange-Mediated Ca2+ Overload during Hypoxia-Reoxygenation in Rat Ventricular Myocytes J. Physiol., August 1, 2003; 550(3): 889 - 898. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Li, V. Williams, L. Liu, H. Chen, T. Sawamura, F. Romeo, and J. L. Mehta Expression of lectin-like oxidized low-density lipoprotein receptors during ischemia-reperfusion and its role in determination of apoptosis and left ventricular dysfunction J. Am. Coll. Cardiol., March 19, 2003; 41(6): 1048 - 1055. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Savelieva and A. John Camm Atrial fibrillation and heart failure: natural history and pharmacological treatment Europace, January 1, 2003; 5(s1): S5 - S19. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Rodriguez and A. Darszon Intracellular sodium changes during the speract response and the acrosome reaction in sea urchin sperm J. Physiol., January 1, 2003; 546(1): 89 - 100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Li, V. Williams, L. Liu, H. Chen, T. Sawamura, T. Antakli, and J. L. Mehta LOX-1 inhibition in myocardial ischemia-reperfusion injury: modulation of MMP-1 and inflammation Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H1795 - H1801. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Miyata, D. P. Zipes, S. Hall, and M. Rubart KB-R7943 Prevents Acute, Atrial Fibrillation-Induced Shortening of Atrial Refractoriness in Anesthetized Dogs Circulation, September 10, 2002; 106(11): 1410 - 1419. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Reuter, S. A. Henderson, T. Han, T. Matsuda, A. Baba, R. S. Ross, J. I. Goldhaber, and K. D. Philipson Knockout Mice for Pharmacological Screening: Testing the Specificity of Na+-Ca2+ Exchange Inhibitors Circ. Res., July 26, 2002; 91(2): 90 - 92. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
