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Review

Is timing everything? Therapeutic potential of modulators of cardiac Na+ transporters

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Pages 1123-1142 | Published online: 02 Mar 2005

Bibliography

  • KARMAZYN M, GAN TG, HUMPHREYS RA, YOSHIDA H, KUSUMOTO K: The myocardial Na+ -/ H+ exchange. Structure, regulation, and its role in heart disease. Circ. Res. (1999) 85:777–786.
  • •Good background review to the NHE.
  • BLAUSTEIN MP, LEDERER WJ: Sodium/calcium exchange: its physiological implications. Physiol Rev (1999) 79:763–854.
  • •Good background review to the NCX.
  • PHILIPSON KD, NICOLL DA: Sodium- calcium exchange: a molecular perspective. Ann. Rev Physiol (2000) 62:111–133.
  • •Good background review to the NCX.
  • KARMAZYN M, SOSTARIC JV, GAN XT: The myocardial Na+/H+ exchanger: a potential therapeutic target for the prevention of myocardial ischaemic and reperfusion injury and attenuation of postinfarction heart failure. Drugs (2001) 61:375–389.
  • NUMATA M, ORLOWSKI J: Molecularcloning and characterization of a novel (Na+, K+)/H+ exchanger localized to the trans-Golgi network. J. Biol. Chem. (2001) 276:17387–17394.
  • GOYAL S, VAN DEN HEUVEL G, ARONSON PS: Renal expression of novel novel Na+/H+ exchanger isoform NHE8. Am. Physiol Renal. Physiol (2003) 284:F467–F473.
  • AVKIRAN M, HAWORTH RS: Regulation of cardiac Na+/H+ exchanger activity by endogenous ligands. Relevance to ischaemia. Ann. NY Acad. Sci. (1999) 874:335–345.
  • SANDMAN S, YU M, KASCHINA E et al: Differential effects of angiotensin AT1 and AT2 receptors on the expression, translation and function of the Na+-H+ exchanger and Na+-HCO3- symporter in the rat heart after myocardial infarction. J. Am. Coll Cardiol (2001) 37:2154–2165.
  • IMASHASHI K, HASHIMOTO K, YAMAGUCHI H, NISHIMURA T, KUSUOKA H: Alteration of intracellular Na+ during ischemia in diabetic rat hearts: The role of reduced activity in Na+/H+ exchange stunning. I Ma Cell. Cardiol (1998) 30:509–517.
  • RAMASAMY R, SHAEFER S: Inhibition of Na+-H+ exchanger protects diabetic and non-diabetic hearts from ischemic injury: insight into altered susceptibility of diabetic hearts to ischemic injury. Ma Cell. Cardiol (1999) 31:785–797.
  • YASUTAKE M, AVKIRAN M: Exacerbation of reperfusion arrhythmias by alpha 1 adrenergic stimulation: a potential role for receptor mediated activation of sarcolemmal sodium-hydrogen exchange. Cardiovasc. Res. (1995) 29:222–230.
  • YOKOYAMA H, GUNASEGARAM S, HARDING SE, AVKIRAN M: Sarcolemmal Na+/H+ exchanger activity and expression in human ventricular myocardium. Am. Coll. Cardiol (2000) 36:534–540.
  • •Demonstration that NHE1 activity is increased in human heart failure.
  • ENGELHARDT S, HEIN L, KELLER U, KLAMBT K, LOHSE MJ: Inhibition of Na+-H+ exchange prevents hypertrophy, fibrosis, and heart failure in 31-adrenergic receptor transgenic mice. Circ. Res. (2002) 90:814–819.
  • CAMILION DE HURTADO MC, ENNIS IL, PEREZ NG et al: Upregulation of myocardial Na+/H+ exchanger induced by chronic treatment with a selective inhibitor. Ma Cell. Cardiol (2002) 34:1539–1547.
  • KARMAZYN M: Amiloride enhances postischemic ventricular recovery: possible role of Na+-H+exchange. Am. J. Physiol (1988) 255:H608-H615. First experimental demonstration of beneficial effects of arniloride in ischaemia.
  • KARMAZYN M, RAY M, HAIST JV: Comparative effects of Na+/H+ exchange inhibitors against cardiac injury produced by ischemia/reperfusion, hypoxia/ reoxygenation, and the calcium paradox. Cardiovasc. Pharinacol (1993) 21:172–178.
  • MOFFAT MP, KARMAZYN M: Protective effects of the potent Na/H exchanger inhibitor methylisobutyl amiloride against post-ischemic contractile dysfunction in rats and guinea-pig hearts. J. MM. Cell. Cardiol (1993) 25:959–971.
  • MYERS ML, MATHUR S, LI GH, KARMAZYN M: Sodium-hydrogen exchange inhibitors improve postischemic recovery of function in the perfused rabbit heart. Cardiovasc. Res. (1995) 29:209–214.
  • WEICHERT A, FABER S, JANSEN HW, SCHOLZ W, LANG HJ: Synthesis of the highly selective Na+/H+ exchange inhibitors cariporide mesilate and (3-methanesulfony1-4-piperidino-benzoyfl guanidine methanesulfonate. Arzneimittelforschung (1997) 47:1204–1207.
  • SCHOLZ W, ALBUS U, COUNILLON L: Protective effects of H0E642, a selective sodium-hydrogen exchange subtype 1 inhibitor, on cardiac ischaemia and reperfusion. Cardiovasc. Res. (1995) 29:260–268.
  • SCHOLZ W, ALBUS U, LANG HJ et al.: Hoe 694, a new Na+/H+ exchange inhibitor and its effects in cardiac ischaemia. Br. J. Pharinacol (1993) 109:562–568.
  • SACK S, MOHRI M, SCHWARZ ER et al.: Effects of a new Na+/H+ antiporter inhibition on postischemic reperfusion in pig heart. J. Cardiovasc. Pharinacol (1994) 23:72–78.
  • ROHMANN S, WEYGANDT H, MINCK KO: Preischaemic as well as postischaemic application of a Na+/H+ exchange inhibitor reduces infarct size in pigs. Cardiovasc. Res. (1995) 30:945–951.
  • CHAKRABARTI S, HOQUE AN, KARMAZYN M: A rapid ischemia-induced apoptosis in isolated rat hearts and its attenuation by the sodium-hydrogen exchange inhibitor HOE 642 (cariporide). J. Ma Cell. Cardiol (1997) 29:3169–3174.
  • AYE NN, XUE YX, HASHIMOTO K: Antiarrhythmic effects of cariporide, a novel Na+-H+ exchange inhibitor, on reperfusion ventricular arrhythmias in rat hearts. Eur: Pharinacol (1997) 27:121–127.
  • LINZ W, ALBUS U, CRAUSE P et al.: Dose-dependent reduction of myocardial infarct mass in rabbits by the NHE-1 inhibitor cariporide (HOE 642). Clio. Exp. Hypertens. (1998) 20:733–749.
  • KLEIN HH, BOHLE RM, PICH S et al: Time-dependent protection by Na+/H+ exchange in a regional ischemic, reperfusion porcine heart preparation with low residual blood flow. J. Ma Cell. Cardiol (1998) 30:795–801.
  • HUMPHREYS RA, HAIST JV, CHAKRABARTI S et al.: Orally administered NHE1 inhibitor cariporide reduces acute responses to coronary occlusion and reperfusion. Am. J. Physiol (1999) 276:H749–H757.
  • •Experimental study showing cariporide pretreatment can reduce the severity of ischaemic and reperfusion injury.
  • XU Z, RAO Z, COHEN MV, DOWNEEY JM: Protection from AMP can be added to that from either cariporide or ischemic preconditioning in ischemic rabbit heart. Cardiovasc. Pharmacol (2002) 40:510–518.
  • HENDRIKX M, REGA F, JAMAER L et al.: Na+/H+-exchange inhibition and aprotinin administration: promising tools for myocardial protection during minimally invasive CABG. Eur: j Cardiothorac. Surg. (2001) 19:633–639.
  • GUMINA RJ, MOORE J, SCHELLING P,BEIER N, GROSS GJ: Na+/H+ exchange inhibition prevents endothelial dysfunction after I/R injury. Am. J. Physiol Heart Circ. Physiol (2001) 281:H1260–H1266.
  • GUNMAN-PEREZ A, WESTER RT, ALLEN MC et al.: Discovery of zoniporide: a potent and selective sodium-hydrogen exchanger Type 1 (NHE-1) inhibitor with high aqueous solubility. Bioorg. Med. Chem. Lett. (2001) 11:803–807.
  • MARALA RB, BROWN JA, KONG JX et al.: Zoniporide: a potent and highly selective inhibitor of human Na+/H+ exchanger-1. Eur. Pharmacol (2002) 451:37–41.
  • KNIGHT DR, SMITTH AH, FLYNN DM et al.: A novel sodium-hydrogen exchanger isoform-1 inhibitor, zoniporide, reduces ischemic myocardial injury in vitro and in vivo. J. Pharmacol Exp. Ther. (2001) 297:254–259.
  • GUMINA RJ, MIZUMURA T, BEIER N et al.: A new sodium/hydrogen exchange inhibitor, EMD 85131, limits infarct size in dogs administered before or after coronary artery occlusion. J. Pharmacol Exp. Ther: (1998) 286:175–183.
  • BANNO H, FUJI WARA J, HOSOYA J et al: Effects of MS-31-038, a novel Na+-H+ exchange inhibitor, on the myocardial infarct size in rats after postischemic administration. Arzneimittelforschung (1999) 49:304–310.
  • OHARA F, SUGIMOTO T, YAMAMOTO N et al: Preischemic and postischemic treatment with a new Na+/ H+-exchange inhibitor, FR183998, shows cardioprotective effects in rats with cardiac ischemia and reperfusion. Cardiovasc. Pharmacol (1999) 34:848–856.
  • LORRAIN J, BRIAND V, FAVENNEC E et al.: Pharmacological profile of SL 59.1227, a novel inhibitor of the sodium/ hydrogen exchanger. Br. J. Pharmacol (2000) 131:1188–1194.
  • KUSUMOTO K, IGATA H, ABE A et al.: In vitro and in vivo pharmacology of a structurally novel Na+ -H+ exchange inhibitor, T-162559. Br: J. Pharmacol (2002) 135:1995–2003.
  • WU D, STRASSEN JM, SEIDLER R, DOODS H: Effects of BIIB513 on ischemia-induced arrhythmias and myocardial infarction in anesthetized-rats. Basic Res. Cardiol (2000) 95:449–456.
  • AIHARA K, HISA H, SATO T et al: Cardioprotective effect of TY-12533, a novel Na+/H+ exchange inhibitor, on ischemia/reperfusion injury. Eur. Pharmacol (2000) 404:221–229.
  • KLEIN HH, PICH S, BOHLE RIVI, LINDERT-HEIMBERG, NEBENDAHL K: Na+/H+ exchange inhibitor cariporide attenuates cell injury predominantly during ischemia and not at onset of reperfusion in porcine hearts with low residual blood flow. Circulation (2000) 102:1977–1982.
  • HARTMANN M, DECKING UK: Blocking Na+-H+ exchange by cariporide reduces Na+-overload in ischemia and is cardioprotective. MM. Cell. Cardiol (1999) 31:1985–1995.
  • STROMER H, DE GROOT MC, HORN M et al.: Na+/H+ exchange inhibition with H0E642 improves postischemic recovery due to attenuation of Ca2+ overload and prolonged acidosis on reperfusion. Circulation (2000) 101:2749–2755.
  • HOQUE AN, HAIST JV, KARIVIAZYN M: Na+-H+ exchange inhibition protects against mechanical, ultrastructure, and biochemical impairment induced by low concentrations of lysophosphatidylcholine in isolated rat hearts. Circ. Res. (1997) 80:95–102.
  • MYERS ML, FARHANGKHOEE P, KARIVIAZYN M: Hydrogen peroxide induced impairment of post-ischemic ventricular function is prevented by the sodium-hydrogen exchange inhibitor HOE 642 (cariporide). Cardiovasc. Res. (1998) 40:290–296.
  • SNABAITIS AK, HEARSE DJ, AVKIRAN M: Regulation of sarcolemmal Na+/H+ exchange by hydrogen peroxide in adult rat ventricular myocytes. Cardiovasc. Res. (2002) 53:470–480.
  • YAMAMOTO S, MATSUI K, ITOH N, OHASHI N: The effect of an Na+/H+ exchange inhibitor, SM-20550, on ischemia/reperfusion-induced endothelial dysfunction in isolated perfused rat hearts. Int. J. Tissue React. (2001) 23:1–7.
  • HATTORI R, OTANI H, MORIGUCHI Y et al.: NHE and ICAM-1 expression in hypoxic/reoxygenated coronary microvascular endothelial cells. Am.Physiol Heart Circ. Physic] (2001)280:H2796–H803.
  • THEROUX P, CHAITMAN BR, DANCHIN N et at: Inhibition of the sodium-hydrogen exchanger with cariporide to prevent myocardial infarction in high-risk ischemic situations. Main results of the GUARDIAN trial. Circulation (2000) 102:3032–3038.
  • ••Major clinical trial showing disappointingresult that cariporide has little benefit when administered in unstable angina or non-ST-elevation MI.
  • RUPPRECHT H-J, VOM DAHL J, TERRES W et al.: Cardioprotective effects of the Na+/H+ exchange inhibitor cariporide in patients with acute anterior myocardial infarction undergoing direct PTCA. Circulation (2000) 101:2902–2908.
  • ZEYMER U, SURYAPRANATA H, MONASSIER JP et al.: The Na+/H+ exchange inhibitor eniporide as an adjunct to early reperfusion therapy for acute myocardial infarction. Am. Coll. Cardiol (2001) 38:1644–1650.
  • ••Major trial showing that eniporide isineffective when administered after thrombolytic therapy or prior to angioplasty in acute MI.
  • AVKIRAN M, MARBER MS: Na+/H+ exchange inhibitors for cardioprotective therapy: progress, problems and prospects. J. Am. Coll. Cardiol (2002) 39:747–753.
  • SHARMA A, SINGH M: Effect of ethylisopropyl amiloride, a Na+-H+ exchange inhibitor, on cardioprotective effect of ischaemic and angiotensin preconditioning. MM. Cell. Biochem. (2000) 214:31–38.
  • SHIPOLINI AR, YOKOYAMA H, GALINANES M et al.: Na+/H+ exchanger activity does not contribute to protection by ischemic preconditioning in the isolated rat heart. Circulation (1995) 96:3617–3625.
  • MOSCA SM, CINGOLANI HE: Comparison of the protective effects of ischemic preconditioning and the Na+/H+ ex hanger blockade. Naunyn Schmiedebergs Arch. Pharmacol. (2000) 362:7–13.
  • AYE NN, KOMORI S, HASHIMOTO K: Effects and interaction, of cariporide and preconditioning on cardiac arrhythmias and infarction in rat in vivo. Br. J. Pharmacol. (1999) 127:1048–1055.
  • GUMINA RJ, BUERGER E, EICKMEIER C: Inhibition of the Na+/H+ exchanger confers greater cardioprotection against 90 minutes of myocardial ischemia than ischemic preconditioning in dogs. Circulation (1999) 100:2519–2526.
  • MIURA T, LIU Y, GOTO M et al: Mitochondrial ATP-sensitive K+ channels play a role in cardioproection by Na+-H+ exchange inhibition against ischemia/ reperfusion injury. I Am. Coll. Cardiol (2001) 37:957–963.
  • GUMIRA RJ, BEIER N, SCHELLING P, GROSS GJ: Inhibitors of ischemic preconditioning do no attenuate Na+/H+ exchange inhibitor mediated cardioprotection. Cardiovasc. Pharmacol (2000) 35:949–953.
  • HALE SL, KLONER RA: Effect of combined KATP channel activation and Na+/H+ exchange inhibition on infarct size in rabbits. Am. Physiol Heart Circ. Physic] (2000) 279:H2673–H2677.
  • HAIST JV, HIRST C, KARMAZYN M: Effective protection by NHE-1 inhibition in ischemic and reperfused heart under preconditioning blockade. Am. J. Physic] Heart Circ. Physiol. (2003) 284:H798–H803.
  • GAZMURI RJ, AYOUB IM, HOFFNER E, KOLAROVA JD: Successful ventricular defibrillation by the selective sodium-hydrogen exchanger isoform-1 inhibitor cariporide. Circulation (2001) 104:234–235.
  • •Experimental study showing that cariporide may be useful in cardiac resuscitation.
  • HISHINO K, AVKIRAN M: Effects of moderate hypothermia on sarcolemmal Na+/H+ exchanger activity and its inhibition by cariporide in cardiac ventricular myocytes. Br. J. Pharmacol (2001) 134:1587–1595.
  • SHIPOLINI AR, GALINANES M, EDMONDSON SJ, HEARSE DJ, AVKIRAN M: Na+/H+ exchanger inhibitor NOE-642 improves cardioplegic myocardial preservation under both normothermic and hypothermic conditions. Circulation (1997) 96(Suppl. II):266–273.
  • TRITTO FP, INSERTE J, GARCIA-DORADO D, RUIZ-MEANA M, SOLER-SOLER J: Sodium/hydrogen exchanger inhibition reduces myocardial reperfusion edema after normothermic cardioplegia. Thome. Cardiovasc. Stow. (1998) 115:709–715.
  • COX CS, SAUER H, ALLEN SJ, BUJA LM, LAINE GA: Sodium/hydrogen-exchanger inhibition during cardioplegic arrest and cardiopulmonary bypass: an experimental study. J. Thome. Cardiovasc. Stow. (2002) 139:959–966.
  • FUKUHIRO Y, WOWK M, OU R, ROSENFELDT F, PEPE S: Cardioplegic strategies for calcium control: low Ca2+, high Mg+, citrate, or Na+/H+ exchange inhibitor HOE-642. Circulation (2000) 102(Suppl. III):III-319-III–325.
  • TOYODA Y, KHAN S, CHEN W et al.: Effects of NHE-1 inhibition on cardioprotection and impact on protection by K/Mg cardiopleagia. Ann. Thome. Surg. (2001) 72:836–843.
  • KIM YI, HERIJGERS P, VAN LOMMEL A, VERBEKEN E, FLAMENG W: Na+/H+ exchange inhibition improves post-transplant myocardial compliance in 4-hour stored donor hearts. Cardiovasc. Surg. (1998) 6:67–75.
  • KIM YI, HERIJGERS P, LAYCOCK SK et al.: Na+/H+ exchange inhibition improves long-term myocardial preservation. Ann. Thome. Stow. (1998) 66:436–442.
  • STOWE DF, HEISNERJS, AN J et al: Inhibition of Na+/H+ isoform-1 exchange protects hearts perfused after 6-hour cardioplegic cold storage. Heart Lung Transplant (2002) 21:374–382.
  • YOSHIDA H, KARAMAZYN M: Na±/H+ exchange inhibition attenuates hypertrophy and heart failure in 1-wk postinfarction rat myocardium. Am. J. Physiol Heart Circ. Physiol (2000) 278:H300–H304.
  • •Experimental study showing that cariporide is beneficial prior to MI.
  • KASUMOTO K, HAIST JV, KARMAZYN M: Na+/H+ exchange inhibition reduces hypertrophy and heart failure after myocardial infarction in rats. Am. .1 Physiol Heart Circ. Physiol (2001) 280:H738–H745.
  • SPITZNAGEL H, CHUNG 0, XIA Q-G et al: Cardioprotective effects of the Nei 1-1-F-exchange inhibitor cariporide in infarct-induced heart failure. Cardiovasc. Res. (2000) 46:102–110.
  • LOENNECHEN JP, WISLOFF U, FALCK G, ELLINGSEN 0: Effects of cariporide and losartan on hypertrophy, calcium transients, contractility, and gene expression in congestive heart failure. Circulation (2002) 105:1380–1386.
  • CAMILION DE HURTADO MC, PORTIANSKY EL, PE.REZ NG, REBOLLEDO OR, CONGOLANI HE: Regression of cardiomyocyte hypertrophy in SHR following chronic inhibition of the Na+/H+ exchanger. Cardiovasc. Res. 53.862–868.
  • CINGOLANI HE, REBOLLEDO OR, PORTIANSKY EL, PE.REZ NG, CAMILION DE HURTADO MC: Regression of hypertensive myocardial fibrosis by Na+/H+ exchange inhibition. Hypertension (2003) 41:373–377.
  • CHEN L, GAN XT, HAIST JV et al.: Attenuation of compensatory right ventricular hypertrophy and heart failure following monocrotaline-induced pulmonary vascular injury by the Na+-H±exchange inhibitor cariporide. Pharmacol Exp. Then (2001) 298:469–476.
  • HILEETO D, CUKIERNIK M, MUKHERJEE S et al.: Contributions of endothelin-1 and sodium hydrogen exchanger-1 in the diabetic myocardium. Diabetes Metab. Res. Rev (2002) 18:386–394.
  • KHANDOUDI N, BERNARD M, COZZONE P, FEUVRAY D: Mechanisms of intracellular pH regulation during postischemic reperfusion of diabetic rat hearts. Diabetes (1995) 44:196–202.
  • CHOI I, ROMERO MF, KHANDOUDI N, BRIL A, BORON WF: Cloning and characterization of a human electrogenic Na+-HCO3- cotransporter isoform (hhNBC). Am. .1 Physiol (1999) 276:C576–0584.
  • CHOI I, AALKJAER C, BOULPAEP EL, BORON WF; Cloning, tissue distribution, genomic organization, and functional characteristics of NBC3, a new member of the sodium bicarbonate cotransporter family. Nature (2000) 274:16569–16575.
  • KHANDOUDI N, ALBADINE J, ROBERT P et al: Inhibition of the cardiac electrogenic sodium bicarbonate cotransporter reduces ischemic injury. Cardiovasc. Res. (2001) 52:387–396.
  • BAETZ D, HAWORTH RS, AVKIRAN M, FEUVRAY D: The ERK pathway regulates Na+-HCO3- cotransport activity in adult rat cardiomyocytes. Am. Physiol Heart ChM Physiol (2002) 283:H2102–H2109.
  • REEVES JP, HALE CC: The stoichiometryof the cardiac sodium-calcium exchange system. J. Bio/. Chem. (1984) 259:7733–7739.
  • KIMURA J, MIYAMAE S, NOMA A: Identification of sodium-calcium exchange current in single ventricular cells of guinea-pig. J. Physiol (1987) 384:199–222.
  • FUJIOKA Y, KOMEDA M, MATSUOKA S: Stoichiometry of Na+-Ca2+ exchange in inside-out patches excised from guinea-pig ventricular myocytes. .1 Physiol (2000) 523:339–351.
  • DONG H, DUNN J, LYTTON J: Stoichiometry of the Cardiac Na±/Ca2+ exchanger NCX1.1 measured in transfected HEK cells. Biophys. (2002) 82:1943–1952.
  • NICOLL DA, OTTOLIA M, LU L, LU Y, PHILIPS ON KD: A new topological model of the cardiac sarcolemmal Na+-Ca2+ exchanger. J. Biol. Chem. (1999) 274:910–917.
  • SHIGEKAWA M, IWAMOTO T: Cardiac Na+-Ca2+ exchange: molecular and pharmacological aspects. Circ. Res. (2001) 88:864–876.
  • SHIGEKAWA M, IWAMOTO T, UEHARA A, KITA S: Probing ion binding sites in the Na±/Ca2+ exchanger. Ann. NY Acad. Sci. (2002) 976:19–30.
  • IWAMOTO T, UEHARA A, IMANAGA I,SHIGEKAWA M: The Na+/Ca2+ exchanger NCX1 has oppositely oriented reentrant loop domains that contain conserved aspartic acids whose mutation alters its apparent Ca2+ affinity../. Biol. Chem. (2000) 275:38571–38580.
  • IWAMOTO T, UEHARA A, NAKAMURA TY, IMANAGA I, SHIGEKAWA M: Chimeric analysis of Na(F)/Ca) exchangers NCX1 and NCX3 reveals structural domains important for differential sensitivity to external Ni(2) or Li(±). Biol. Chem. (1999) 274:23094–23102.
  • BERS DM: Excitation-Contraction Coupling and Cardiac Force (2nd Ed.). Kluwer, Dordrecht, The Netherlands (2001).
  • TRAFFORD AW, DIAZ ME, O'NEILL SC, EISNER DA: Integrative analysis of calcium signalling in cardiac muscle. Front. Biosci. (2002) 7:d843–d852.
  • NUSS HB, HOUSER SR: Sodium-calciumexchange-mediated contractions in feline ventricular myocytes. Am. Physiol (1992) 263:H1161–H1169.
  • LEVI AJ, BROOKSBY P, HANCOX JC: A role for depolarisation induced calcium entry on the Na-Ca exchange in triggering intracellular calcium release and contraction in rat ventricular myocytes. Cardiovasc. Res. (1993) 27:1677–1690.
  • KOHOMOTO 0, LEVI AJ, BRIDGE JH: Relation between reverse sodium-calcium exchange and sarcoplasmic reticulum calcium release in guinea pig ventricular cells. Circ. Res. (1994) 74:550–554.
  • MATTIELLO JA, MARGULIES KB, JEEVANANDAM V, HOUSER SR: Contribution of reverse-mode sodium-calcium exchange to contractions in failing human left ventricular myocytes. Cardiovasc. Res. (1998) 37:424–431.
  • SIPIDO KR, MAES M, VAN DE WERF F: Low efficiency of Ca2+ entry through the Na(+)-Ca2+ exchanger as trigger for Ca2+ release from the sarcoplasmic reticulum. A comparison between L-type Ca2+ current and reverse-mode Na(+)-Ca2+ exchange. Circ. Res. (1997) 81:1034–1044.
  • YANG Z, PASCAREL C, STEELE DS, KOMUKAI K, BRETTE F, ORCHARD CH: Na+-Ca2+ exchange activity is localized in the T-tubules of rat ventricular myocytes. Circ. Res. (2002) 91:315–322.
  • NOBLE D, NOBLE SJ, BETT GC et al.: The role of sodium-calcium exchange during the cardiac action potential. Ann. N 11.- Acad. Sci. (1991) 639:334–353.
  • JANVIER NC, BOYETT MR: The role of Na-Ca exchange current in the cardiac action potential. Cardiovasc. Res. (1996) 32:69–84.
  • JANVIER NC, HARRISON SM, BOYETT MR: The role of inward Na()-Ca2+ exchange current in the ferret ventricular action potential.," Physic] (1997) 498:611–625.
  • RIGG L, TERRAR DA: Possible role of calcium release from the sarcoplasmic reticulum in pacemaking in guinea-pig sino-atrial node. Exp. Physic] (1996) 81:877–880.
  • BOGDANOV KY, VINOGRADOVA TM, LAKATTA EG: Sinoatrial nodal cell ryanodine receptor and Na(+)-Ca(2+) exchanger: molecular partners in pacemaker regulation. Circ. Res. (2001) 88:1254–1258.
  • HONJO H, INADA S, LANCASTER MK et al.: Sarcoplasmic reticulum Ca2+ release is not a dominating factor in sinoatrial node pacemaker activity. Circ. Res. (2003) 92:e41–e44.
  • LAKATTA EG, MALTSEV VA, BOGDANOV KY, STERN MD, VINOGRAD OVA TM: Cyclic variation of intracellular calcium: a critical factor for cardiac pacemaker cell dominance. Circ. Res. (2003) 92:e45–e50.
  • PERCHENET L, HINDE AK, PATEL KC, HANCOX JC, LEVI AJ: Stimulation of Na/Ca exchange by the beta-adrenergic/protein kinase A pathway in guinea-pig ventricular myocytes at 37 degrees C. Pflugers Arch. (2000) 439:822–828.
  • RUKNUDIN A, HE S, LEDERER WJ, SCHULZE DH: Functional differences between cardiac and renal isoforms of the rat Na+-Ca2+ exchanger NCX1 expressed in Xenopus oocytes. Physic] (2000) 529:599–610.
  • ZHANG YH, HINDE AK, HANCOX JC: Anti-adrenergic effect of adenosine on Na(+)-Ca(2+) exchange current recorded from guinea-pig ventricular myocytes. Cell Calcium (2001) 29:347–358.
  • STENGL M, MUBAGWA K, CARMELIET E, FLAMENG W: Phenylephrine-induced stimulation of Nei Ca2+ exchange in rat ventricular myocytes. Cardiovasc. Res. (1998) 38:703–710.
  • ZHANG YH, JAMES AF, HANCOX JC: Regulation by endothelin-1 of Na+-Ca2+ exchange current (INaCa) from guinea-pig isolated ventricular myocytes. Cell Calcium (2001) 30:351–360.
  • AIELLO EA, VILLA-ABRILLE MC, CINGOLANI HE: Autocrine stimulation of cardiac Na(+)-Ca(2+) exchanger currents by endogenous endothelin released by angiotensin II. Circ. Res. (2002) 90:374–376.
  • ZHANG YH, HANCOX JC: Evidence for a modulatory effect of external potassium ions on ionic current mediated by the cardiac Na+-Ca2+ exchanger. Cell Calcium (2003) 33:49–58.
  • CHO CH, KIM SS, JEONG MJ, LEE CO, SHIN HS: The Na+-Ca2+ exchanger is essential for embryonic heart development in mice. Ma Cells (2000) 10(6):712–722.
  • WAKIMOTO K, KOBAYASHI K, KUR0-0 M et al.: Targeted disruption of Na+/Ca2+ exchanger gene leads to cardiomyocyte apoptosis and defects in heartbeat. J. Biol. Chem. (2000) 275:36991–36998.
  • LEDERER WJ, ISIEN RW: Transient inward current underlying arrhythmogenic effects of cardiotonic steroids in Purkinje fibres. J. Physiol (1976) 263:73–100.
  • EISNER DA, LEDERER WJ: Inotropic and arrhythmogenic effects of potassium-depleted solutions on mammalian cardiac muscle., " Physiol (1979) 294:255–277.
  • EISNER DA, LEDERER WJ, SHEU SS: The role of intracellular sodium activity in the anti-arrhythmic action of local anaesthetics in sheep Purkinje fibres. J. Physic] (1983) 340:239–257.
  • FOZZARD HA: Afterdepolarizations and triggered activity. Basic Res. Cardiol (1992) 87\(Suppl. 2):105–113.
  • LEVI AJ, DALTON GR, HANCOX JC et al.: Role of intracellular sodium overload in the genesis of cardiac arrhythmias. Cardiovasc. Electrophysiol (1997) 8:700–721.
  • EGDELL RM, MACLEOD KT: Calcium extrusion during aftercontractions in cardiac myocytes: the role of the sodium-calcium exchanger in the generation of the transient inward current. J. MM. Cell. Cardiol (2000) 32:85–93.
  • VERKERK AO, VELDKAMP MW, BAARTSCHEER et al.: A Ionic mechanism of delayed after depolarizations in ventricular cells isolated from human end-stage failing hearts. Circulation (2001) 104:2728-2733. Experimental study showing a role for NCX in arrhythmogenic current and DADs in ventricular cells from failing human hearts.
  • KENT RL, ROZICH JD, MCCOLLAM PL et al.: Rapid expression of the Na(+)-Ca2+ exchanger in response to cardiac pressure overload. Am. J. Physic] (1993) 265:H1024–H1029.
  • FLESCH M, SCHWINGER RH, SCHIFFER F et al: Evidence for functional relevance of an enhanced expression of the Na(+)-Ca2+ exchanger in failing human myocardium. Circulation (1996) 94:992–1002.
  • •Experimental study providing evidence for functional relevance of raised NCX expression in failing human heart tissue.
  • STUDER R, REINECKE H,VETTER R, HOLTZ J, DREXLER H: Expression and function of the cardiac Na+/Ca2+ exchanger in postnatal development of the rat, in experimental-induced cardiac hypertrophy and in the failing human heart. Basic Res. Carcliol (1997) 92\(Suppl. 0:53–58.
  • AHMMED GU, DONG PH, SONG G et al.: Changes in Ca(2+) cycling proteins underlie cardiac action potential prolongation in a pressure-overloaded guinea pig model with cardiac hypertrophy and failure. Circ. Res. (2000) 86:558–570.
  • POGWIZD SM, QI M, YUAN W, SAMAREL AM, BERS DM: Upregulation of Na+/Ca2+ exchanger expression and function in an arrhythmogenic rabbit model of heart failure. Circ. Res. (1999) 85:1009–1019.
  • BERS DM, POGWIZD SM, SCHLOTTHAUER K: Upregulated Na/Ca exchange is involved in both contractile dysfunction and arrhythmogenesis in heart failure. Basic Res. Cardiol (2002) 97\(Suppl. 0:136–142.
  • SIPIDO KR, VOLDERS PG, DE GROOT SH et al.: Enhanced Ca2+ release and Na+/Ca2+ exchange activity in hypertrophied canine ventricular myocytes: potential link between contractile adaptation and arrhythmogenesis. Circulation (2000) 102:2137–2144.
  • WANG Z, NOLAN B, KUTSCHKE W, HILL JA: Na+-Ca2+ exchanger remodeling in pressure overload cardiac hypertrophy. J. Biol. Chem. (2001) 276:17706–17711.
  • SIPIDO KR, VOLDERS PG, VOS MA, VERDONCK F: Altered Na/Ca exchange activity in cardiac hypertrophy and heart failure: a new target for therapy? Cardiovasc. Res. (2002) 53:782–805.
  • •Useful review of NCX in hypertrophy and heart failure.
  • HAIGNEY MC, MIYATA H, LAKATTA EG, STERN MD, SILVERMAN HS: Dependence of hypoxic cellular calcium loading on Na(+)-Ca2+ exchange. Circ. Res. (1992) 71:547–557.
  • HAIGNEY MC, LAKATTA EG, STERN MD, SILVERMAN HS: Sodium channel blockade reduces hypoxic sodium loading and sodium-dependent calcium loading. Circulation (1994) 90:391–399.
  • PHILIPSON KD, BERSOHN MM, NISHIMOTO AY: Effects of pH on Nat-Ca2+ exchange in canine cardiac sarcolemmal vesicles. Circ. Res. (1982) 50:287–293.
  • DOERING AE, LEDERER WI: The mechanism by which cytoplasmic protons inhibit the sodium-calcium exchanger in guinea-pig heart cells. 1 Physic] (1993) 466:481–499.
  • VAN WAGONER DR, BOND M: Reperfusion Arrhythmias: new insights into the role of the Na+/Ca2+ exchanger. J. Mel Cardiol (2001) 33:2071–2074.
  • GOLDHABER II: Free radicals enhance Na+/Ca2+ exchange in ventricular myocytes. Am. Physic] (1996) 271:H823–H833.
  • WOODCOCK EA, ARTHUR IF, HARRISON SN, GAO XM, DU XI: Reperfusion-induced ins(1,4,5)p(3)generation and arrhythmogenesis require activation of the Na+/Ca2+ exchanger." Mel Cell. Cardiol (2001) 33:1861–1869.
  • ZEITZ 0, MAASS AE, VAN NGUYEN P et al: Hydroxyl radical-induced acute diastolic dysfunction is due to calcium overload via reverse-mode Na(+)-Ca(2+) exchange. Circ. Res. (2002) 90:988–995.
  • KIMURA J, WATANABE Y, LI L, WATANO T: Pharmacology of Na+/Ca2+ exchanger. Ann. NY Acad. Sci. (2002) 976:513–519.
  • EGGER M, RUKNUDIN A, LIPP P et al: Functional expression of the human cardiac Na+/Ca2+ exchanger in Sf9 cells: rapid and specific Ni2+ transport. Cell Calcium (1999) 25:9–17.
  • HINDE AK, PERCHENET L, HOBAI IA, LEVI Al, HANCOX IC: Inhibition of Na! Ca exchange by external Ni2+ in guinea-pig ventricular myocytes at 37 degrees C, dialysed internally with cAMP-free and cAMP-containing solutions. Cell Calcium (1999) 25:321–331.
  • SIEGL PK, CRAGOE EJ Jr, TRUMBLE MJ, KACZOROWSKI GJ: Inhibition of Na+/Ca2+ exchange in membrane vesicle and papillary muscle preparations from guinea pig heart by analogs of amiloride. Proc. Natl. Acad. Sci.USA (1984) 81:3238–3242.
  • LIPP P, POTT L: Voltage dependence of sodium-calcium exchange current in guinea-pig atrial myocytes determined by means of an inhibitor.' Physic] (1988) 403:355–366.
  • POGWIZD SM: Clinical potential of sodium-calcium exchanger inhibitors as antiarrhythmic agents. Drugs (2003) 63:439–542.
  • •Useful, recent article considering potential of NCX inhibition.
  • WATANABE Y, KIMURA J: Blocking effect of bepridil on Na+/Ca2+ exchange current in guinea pig cardiac ventricular myocytes. fpn..1. Pharmacol (2001) 85:370–375.
  • WATANABE Y, IWAMOTO T, SHIGEKAWA M, KIMURA J: Inhibitory effect of aprindine on Na+/Ca2+ exchange current in guinea-pig cardiac ventricular myocytes. Br. J. Pharmacol (2002) 136:361–366.
  • ZHANG YH, HANCOX IC: Mode-dependent inhibition by quinidine of Na+-Ca2+ exchanger current from guinea-pig isolated ventricular myocytes. Clio. Exp. Pharmacol Physic] (2002) 29:777–781.
  • WATANABE Y, KIMURA J: Inhibitory effect of amiodarone on Na(+)/Ca(2+) exchange current in guinea-pig cardiac myocytes. Br. J. Pharmacol (2000) 131:80–84.
  • WATANABE Y, MATSUOKA I, KIMURA J: Chronic administration of amiodarone does not affect Na+/Ca2+ exchange current in guinea pig cardiac ventricular myocytes. fpn. Pharmacol (2002) 90:21–27.
  • NICOLL DA, LONGONI S, PHILIPSON KD: Molecular cloning and functional expression of the cardiac sarcolemmal Na+-Ca2+ exchanger. Science (1990) 250:562-565. Landmark study, cloning and sequencing of cardiac NCX.
  • LI Z, NICOLL DA, COLLINS A et al.: Identification of a peptide inhibitor of the cardiac sarcolemmal Na+-Ca2+ exchanger. J. Biol. Chem. (1991) 266:1014–1020.
  • •First paper on XIP
  • CHIN TK, SPITZER KW, PHILIPSON KD, BRIDGE JH: The effect of exchanger inhibitory peptide (XIP) on sodium-calcium exchange current in guinea pig ventricular cells. Circ. Res. (1993) 72:497–503.
  • KOHOMOTO 0, LEVI AJ, BRIDGE JH: Relation between reverse sodium-calcium exchange and sarcoplasmic reticulum calcium release in guinea pig ventricular cells. Circ. Res. (1994) 74:550–554.
  • KHANANSHVILI D, SHAULOV G, WEIL-MASLANSKY E, BAAZOV D: Positively charged cyclic hexapeptides, novel blockers for the cardiac sarcolemma Na+-Ca2+ exchanger. J. Biol. Chem. (1995) 270:16182–16188.
  • •First description of cyclic hexapeptide NCX inhibitors.
  • KHANANSHVILI D, BAAZOV D, WEIL-MASLANSKY E, SHAULOV G, MESTER B: Rapid interaction of FRCRCFa with the cytosolic side of the cardiac sarcolemmal Na-Ca exchanger blocks the ion-transport without preventing the binding of either Na or Ca. Biochemistry (1996) 35:15933–15940.
  • KHANANSHVILI D, MESTER B, SALTOUN M et al: Inhibition of the cardiac sarcolemma Na-Ca exchanger by conformationally constrained small cyclic peptides. Mel Pharmacol (1997) 51:126–131.
  • HOBAI IA, KHANANSHVILI D, LEVI Al: The peptide TRCRCFa', dialysed intracellularly, inhibits the Na/Ca exchange in rabbit ventricular myocytes with high affinity. Pflugers Arch. (1997) 433:455–463.
  • MESZAROS J, KHANANSHVILI D, HART G: Mechanisms underlying delayed afterdepolarizations in hypertrophied left ventricular myocytes of rats. Am. J. Physic] (2001) 281:H903–H914.
  • CONVERY MK, LEVI Al, KHANANSHVILI D, HANCOX JC: Actions of myristyl-FRCRCFa, a cell-permeant blocker of the cardiac sarcolemmal Na-Ca exchanger, tested in rabbit ventricular myocytes. Pflugers Arch. (1998) 436:581–590.
  • IWAMOTO T, WATANO T, SHIGEKAWA M: A novel isothiourea derivative selectively inhibits the reverse mode of Na+/Ca2+ exchange in cells expressing NCX1. J. Biol. Chem. (1996) 271:22391–22397.
  • •First report of KB-R7943.
  • WATANO T, KIMURA J, MORITA T, NAKANISHI H: A novel antagonist, No. 7943, of the Na+/Ca2+ exchange current in guinea-pig cardiac ventricular cells. Br. J. Pharmacol(1996) 119:555–563.
  • KIMURA J, WATANO T, KAWAHARA M, SAKAI E, YATABE J: Direction-independent block of bi-directional Na+/Ca2+ exchange current by KB-R7943 in guinea-pig cardiac myocytes. Br: J. Pharmacol (1999) 128:969–974.
  • LI L, KIMURA J: Effect of KB-R7943 on oscillatory Na+/Ca2+ exchange current in guinea pig ventricular myocytes. Ann. NY Acad. Sci. (2002) 976:539–542.
  • LADILOV Y, HAFFNER S, BALSER-SCHAFER C, MAXEINER H, PIPER HM: Cardioprotective effects of KB-R7943: a novel inhibitor of the reverse mode of Na+/Ca2+ exchanger. Am. Physic] (1999) 276:H1868–H1876.
  • •Experimental study showing cardioprotective effects of KB-R7943.
  • SCHAFER C, LADILOV Y, INSERTE J et al.: Role of the reverse mode of the Na+/ Ca2+ exchanger in reoxygenation-induced cardiomyocyte injury. Cardiovasc. Res. (2001) 51:241–250.
  • •Experimental study showing cardioprotective effects of KB-R7943.
  • SEKI S, TANIGUCHI M, TAKEDA H et al.: Inhibition by KB-R7943 of the reverse mode of the Na+/Ca2+ exchanger reduces Ca2+ overload in ischemic-reperfused rat hearts. Circ. J. (2002) 66:390–396.
  • MUKAI M, TERADA H, SUGIYAMA S, SATOH H, HAYASHI H: Effects of a selective inhibitor of Na+/Ca2+ exchange, KB-R7943, on reoxygenation-induced injuries in guinea pig papillary muscles. Cardiovasc. Pharmacol (2000) 35:121–128.
  • ELIAS CL, LUKAS A, SHURRAW S et al: Inhibition of Na+/Ca2+ exchange by KB-R7943: transport mode selectivity and antiarrhythmic consequences. Am. Physic] (2001) 281:H1334–H1345.
  • MIYAMOTO S, ZHU BM, KAMIYA K, NAGASAWA Y, HASHIMOTO K: KB-R7943, a Na(+)/Ca(2+) Exchange Inhibitor, Does Not Suppress Ischemia/Reperfusion Arrhythmias nor Digitalis Arrhythmias in Dogs. fpn. Pharmacol (2002) 90:229–235.
  • SATOH H, GINSBURG KS, QING K et al.: KB-R7943 block of Ca(2+) influx via Na(+)/Ca(2+) exchange does not alter twitches or glycoside inotropy but prevents Ca(2+) overload in rat ventricular myocytes. Circulation (2000) 101:1441–1446.
  • KUROGOUCHI F, FURUKAWA Y, ZHAO D et al.: A Na+/Ca2+ exchanger inhibitor, KB-R7943, caused negative inotropic responses and negative followed by positive chronotropic responses in isolated, blood-perfused dog heart preparations. fpn. Pharmacol (2000) 82:155–163.
  • YAMAMURA K, TANI M, HASEGAWA H, GEN W: Very low dose of the Na(+)/Ca(2+) exchange inhibitor, KB-R7943, protects ischemic reperfused aged Fischer 344 rat hearts: considerable strain difference in the sensitivity to KB-R7943. Cardiovasc. Res. (2001) 52:397–406.
  • MATSUMOTO T, MIURA T, MIKI T, GENDA S, SHIMAMOTO K: Blockade of the Na+-Ca2+ exchanger is more efficient than blockade of the Na+-H+ exchanger for protection of the myocardium from lethal reperfusion injury. Cardiovasc. Drugs Ther: (2002) 16:295–301.
  • ••Experimental study comparing beneficialeffect of NCX blockade with KB-R7943 with NHE inhibition with cariporide.
  • PINTADO AJ, HERRERO CJ, GARCIA AG, MONTIEL C: The novel Na(+)/Ca(2+) exchange inhibitor KB-R7943 also blocks native and expressed neuronal nicotinic receptors. Br. J. Pharmacol (2000) 130:1893–1902.
  • MATSUDA T, ARAKAWA N, TAKUMA K et al.: SEA0400, a novel and selective inhibitor of the Na+-Ca2+ exchanger, attenuates reperfusion injury in the in vitro and in vivo cerebral ischemic models. J. Pharmacol Exp. Ther. (2001) 298:249–256.
  • •First study of SEA0400.
  • TANAKA H, NISHIMARU K, AIKAWA T et al: Effect of SEA0400, a novel inhibitor of sodium-calcium exchanger, on myocardial ionic currents.Br. J. Pharmacol (2002) 135:1096–1100.
  • REUTER H, HENDERSON SA, HAN T et al.: Knockout mice for pharmacological screening: testing the specificity of Na+-Ca2+ exchange inhibitors. Circ. Res. (2002) 91:90–92.
  • MAGEE WP, DESHMUKH G, DENINNO MP et al.: Differing cardioprotective efficacy of the Na+/Ca2+ exchanger inhibitors SEA0400 and KB-R7943. Am. J. Physiol (2003) 284:H903–H910.
  • ••Experimental study comparingcardioprotection with KB-R7943 and SEA0400.
  • TAKAHASHI K, TAKAHASHI T, SUZUKI T et al.: Protective effects of SEA0400, a novel and selective inhibitor of the Na+/Ca2+ exchanger, on myocardial ischemia-reperfusion injuries. Eur: Pharmacol (2003) 458:155–162.
  • •Experimental report of cardioprotection by SEA0400.
  • AHMAD S, DOWEYKO LM, DUGAR S et al.: Arylcyclopropanecarboxyl guanidine as novel, potent, and selective inhibitors of the sodium hydrogen exchanger isoform-1. J. Med. Chem. (2001) 44:3302–3310.
  • TOURET N, TANNEUR V, GODART H et al.: Characterization of sabiporide, a new NHE-1 inhibitor exhibiting slow dissociation kinetics and cardioprotective effects. Eur. Pharmacol (2003) 459:151–158.
  • AVKIRAN M: Protection of the ischaemic myocardium by Na+/I-I+ exchange inhibitors: potential mechanisms of action. Basic Res. Cardiol (2001) 96:306–311.
  • INSERTE J, GARCIA-DORADO D, RUIZ-MEANA M et al.: Effect of inhibition of Na(+)/Ca(2+) exchanger at the time of myocardial reperfusion on hypercontracture and cell death. Cardiovasc. Res. (2002) 55:739–748.

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