Characterization of gap junction remodeling in epicardial border zone of healing canine infarcts and electrophysiological effects of partial reversal by rotigaptide

Circulation: Arrhythmia and Electrophysiology

Volumn 4, Issue 3, 2011, Pages 344-351

  Macia, Ester ^a   Dolmatova, Elena ^b   Cabo, Candido ^a   Sosinsky, Alexandra Z ^b   Dun, Wen ^a   Coromilas, James ^a   Ciaccio, Edward J ^a   Boyden, Penelope A ^a   Wit, Andrew L ^a   Duffy, Heather S ^b  

^a Howard Hughes Medical Institute   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Arrhythmias; Gap junctions; Myocardial infarction; Remodeling

Indexed keywords

CONNEXIN 43; ROTIGAPTIDE; SERINE; OLIGOPEPTIDE;

ANTIARRHYTHMIC ACTIVITY; ARTICLE; CONTROLLED STUDY; DOG; EPICARDIAL BORDER ZONE; EPICARDIUM; GAP JUNCTION; HEALING; HEART CONDUCTION; HEART ELECTROPHYSIOLOGY; HEART INFARCTION; HEART STIMULATION; HEART VENTRICLE TACHYCARDIA; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEPLETION; PROTEIN PHOSPHORYLATION; ANIMAL; CELL JUNCTION; COMPARATIVE STUDY; CONVALESCENCE; DISEASE MODEL; DRUG EFFECT; ELECTROPHYSIOLOGY; HEART MUSCLE CONDUCTION SYSTEM; METABOLISM; PATHOPHYSIOLOGY; PERICARDIUM; PHYSIOLOGY;

ANIMALS; DISEASE MODELS, ANIMAL; DOGS; ELECTROPHYSIOLOGICAL PHENOMENA; GAP JUNCTIONS; HEART CONDUCTION SYSTEM; MYOCARDIAL INFARCTION; OLIGOPEPTIDES; PERICARDIUM; RECOVERY OF FUNCTION; TACHYCARDIA, VENTRICULAR;

EID: 80052308121     PISSN: 19413149     EISSN: 19413084     Source Type: Journal    
DOI: 10.1161/CIRCEP.110.959312     Document Type: Article

References (43)

1. Dillon S, Allessie M, Ursell PC, Wit AL. Influence of anisotropic tissue structure on reentrant circuits in the subepicardial border zone of subacute canine infarcts. Circ Res. 1988;63:182-206.
2. Peters NS, Coromilas J, Severs NJ, Wit AL. Disturbed connexin43 gap junction distribution correlates with the location of reentrant circuits in the epicardial border zone of healing canine infarcts that cause ventricular tachycardia. Circulation. 1997;95:988-996. (Pubitemid 27091545)
3. Severs NJ, Bruce AF, Dupont E, Rothery S. Remodeling of gap junctions and connexin expression in diseased myocardium. Cardiovasc Res. 2008; 80:9-19.
4. Lampe PD, Cooper CD, King TJ, Burt JM. Analysis of connexin43 phosphorylated at S325, S328 and S330 in normoxic and ischemic heart. J Cell Sci. 2006;119:3435-3442. (Pubitemid 44405227)
5. Solan JL, Lampe PD. key connexin 43 phosphorylation events regulate the gap junction life cycle. J Membrane Biol. 2007;217:35-41. (Pubitemid 350160003)
6. Beardslee MA, Lerner DL, Tadros PN, Laing JG, Beyer EC, Yamada KA, Kleber AG, Schuessler RB, Saffitz JE. Dephosphorylation and intracellular redistribution of ventricular connexin43 during electrical uncoupling induced by ischemia. Circ Res. 2000;87:656-662.
7. Solan JL, Lampe PD. Connexin43 phosphorylation: structural changes and biological effects. Biochem J. 2009;419:261-272.
8. Saez JC, Berthoud VM, Branes MC, Martinez AD, Beyer EC. Plasma membrane channels formed by connexins: their regulation and functions. Physiol Rev. 2003;1359-1400. (Pubitemid 37222275)
9. Xing D, Kjølbye AL, Nielsen MS, Petersen JS, Harlow KW, Holstein-Rathlou NH, Martins JB. ZP123 increases gap junctional conductance and prevents reentrant ventricular tachycardia during myocardial ischemia in open chest dogs. J Cardiovasc Electrophysiol. 2003;14:510-520. (Pubitemid 36583913)
10. Hennan JK, Swillo RE, Morgan GA, Keith JC, Schaub RG, Smith RP, Feldman HS, Haugan K, Kantrowitz J, Wang PJ, Abu-Qare A, Butera J, Larsen BD, Crandall DL. Rotigaptide (ZP123) prevents spontaneous ventricular arrhythmias and reduces infarct size during myocardial ischemia/reperfusion injury in open-chest dogs. JPET. 2006;317:236-243.
11. Axelsen LN, Stahlhut M, Mohammed S, Larsen BD, Nielsen MS, Holstein-Rathlou N-H, Andersen S, Jensen ON, Hennan JK, Kjølbye AL. Identification of ischemia-regulated phosphorylation sites in connexin43: a possible target for the antiarrhythmic peptide analogue rotigaptide (ZP123). J Mol Cell Cardiol. 2006;40:790-798. (Pubitemid 43817040)
12. Coromilas J, Saltman AE, Waldecker B, Dillon SM, Wit AL. Electrophysiological effects of flecainide on anisotropic conduction and reentry in infarcted canine hearts. Circulation. 1995;91:2245-2263.
13. Cabo C, Yao J, Boyden PA, Chen S, Hussain W, Duffy HS, Ciaccio EJ, Peters NS, Wit AL. Heterogeneous gap junction remodeling stabilizes reentrant circuits in the epicardial border zone of the healing canine infarct. Cardiovasc Res. 2006;72:242-249.
14. Pu J, Boyden PA. Alterations of Na+ currents in myocytes from epicardial border zone of the infarcted heart: a possible ionic mechanism for reduced excitability and postrepolarization refractoriness. Circ Res. 1997 81:110-119. (Pubitemid 27272989)
15. Kieken F, Mutsaers N, Dolmatova E, Virgil K, Wit AL, Kellezi A, Hirst-Jensen BJ, Duffy HS, Sorgen PL. Structural and molecular mechanisms of gap junction remodeling in epicardial border zone myocytes following myocardial infarction. Circ Res. 2009;104:1100-1112.
16. Haugan K, Olsen KB, Hartvig L, Petersen JS, Holstein-Rathlou NH, Hennan JK, Nielsen MS. The antiarrhythmic peptide analog ZP123 prevents atrial conduction slowing during metabolic stress. J Cardiovasc Electrophysiol. 2005;16:537-545. (Pubitemid 40632487)
17. Lampe PD, TenBroek EM, Burt JM, Kurata WE, Johnson RG, Lau AF. Phosphorylation of connexin43 on serine368 by protein kinase C regulates gap junctional communication. J Cell Biol. 2000;126:1503-1512. (Pubitemid 30437622)
18. Lampe PD, Lau AF. The effects of connexin phosphorylation on gap junctional communication. Int J Biochem Cell Biol. 2004;36:1171-1186. (Pubitemid 38515659)
19. Kleber AG, Riegger CB, Janse MJ. Electrical uncoupling and increase of extracellular resistance after induction of ischemia in isolated, arterially perfused rabbit papillary muscle. Circ Res. 1987;61:271-279. (Pubitemid 17137122)
20. Procida K, Jørgensen L, Schmitt N, Delmar M, Taffet SM, Holstein-Rathlou N-H, Nielsen MS, Braunstein TH. Phosphorylation of connexin43 on serine 306 regulates electrical coupling. Heart Rhythm. 2009;6:1632-1638.
21. Bao X, Reuss L, Altenberg GA. Regulation of purified and reconstituted connexin 43 hemichannels by protein kinase C-mediated phosphorylation of serine 368. J Biol Chem. 2004;279:20058-20066. (Pubitemid 38623450)
22. Solan JL, Lampe PD. Connexin phosphorylation as a regulatory event linked to gap junction channel assembly. Biochim Biophys Acta. 2005; 1711:154-163. (Pubitemid 40799290)
23. Ek-Vitorin JF, King TJ, Heyman NS, Lampe PD, Burt JM. Selectivity of connexin 43 channels is regulated through protein kinase C-dependent phosphorylation. Circ Res. 2006;98:1498-1505. (Pubitemid 44297072)
24. Solan JL, Marquez-Rosado L, Sorgen PL, Thornton PJ, Gafken PR, Lampe PD. Phosphorylation at S365 is a gatekeeper event that changes the structure of Cx43 and prevents down-regulation by PKC. J Cell Biol. 2007;179:1301-1309. (Pubitemid 350277746)
25. Laird DW. Connexin phosphorylation as a regulatory event linked to gap junction internalization and degradation. Biochim Biophys Acta. 2005; 1711:172-182. (Pubitemid 40799292)
26. Yao J-A, Hussain W, Patel P, Peters NS, Boyden P, Wit AL. Remodeling of gap junctional channel function in epicardial border zone of healing canine infarcts. Circ Res. 2003;92:437-443. (Pubitemid 36298204)
27. Danik SB, Liu F, Zhang J, Suk HJ, Morley GE, Fishman GI, Gutstein DE. Modulation of cardiac gap junction expression and arrhythmic susceptibility. Circ Res. 2004;95:1035-1041. (Pubitemid 39532334)
28. Gardner PI, Ursell PC, Fenoglio JJ Jr, Wit AL. Electrophysiologic and anatomic basis for fractionated electrograms recorded from chronically ischemic and infarcted regions of the heart. Circulation. 1985;72: 596-611. (Pubitemid 15242254)
29. Gough WB, Mehra R, Restivo M, Zeiler RH, El-Sherif N. Reentrant ventricular arrhythmias in the late myocardial infarction period in the dog: correlation of activation and refractory maps. Circ Res. 1985;57: 432-442. (Pubitemid 16217986)
30. Lesh MD, Pring M, Spear JF. Cellular uncoupling can unmask dispersion of action potential duration in ventricular myocardium: a computer modeling study. Circ Res. 1989;65:1426-1440. (Pubitemid 19281727)
31. Tan RC, Joyner RW. Electrotonic influences on action potentials from isolated ventricular cells. Circ Res. 1990;67:1071-1081. (Pubitemid 20368004)
32. Spitzer KW, Pollard AE, Yang L, Zaniboni M, Cordeiro JM, Huelsing DJ. Cell-to-cell electrical interactions during early and late repolarization. J Cardiovasc Electrophysiol. 2006;17:S8-S14.
33. Anyukhovsky EP, Sosunov EA, Rosen MR. Regional differences in electrophysiological properties of epicardium, midmyocardium, and endocardium: in vitro and in vivo correlations. Circulation. 1996;94: 1981-1988. (Pubitemid 26349314)
34. Akar FG, Rosenbaum DS. Transmural electrophysiological heterogeneities underlying arrhythmogenesis in heart failure. Circ Res. 2003;93: 638-645. (Pubitemid 37222160)
35. Eloff BC, Gilat E, Wan X, Rosenbaum DS. Pharmacological modulation of cardiac gap junctions to enhance cardiac conduction: evidence supporting a novel target for antiarrhythmic therapy. Circulation. 2003;108: 3157-3163. (Pubitemid 38031807)
36. Kjølbye AL, Dikshteyn M, Eloff BC, Deschenes I, Rosenbaum DS. Maintenance of intercellular coupling by the antiarrhythmic peptide rotigaptide suppresses arrhythmogenic discordant alternans. Am J Physiol Heart Circ Physiol. 2008;294:H41-H49.
37. Guerra JM, Everett TH IV, Lee KW, Wilson E, Olgin JE. Effects of the gap junction modifier rotigaptide (ZP123) on atrial conduction and vulnerability to atrial fibrillation. Circulation. 2006;114:110-118. (Pubitemid 44420742)
38. Kjølbye AL, Knudsen CB, Jepsen T, Larsen BD, Petersen JS. Pharmacological characterization of the new stable antiarrhythmic peptide analog Ac-D-Tyr-DPro-D-Hyp-Gly-D-Ala-Gly-NH2 (ZP123): in vivo and in vitro studies. J Pharmacol Exp Ther. 2003;306:1191-1199. (Pubitemid 37028306)
39. Dhein S, Larsen BD, Petersen JS, Mohr FW. Effects of the new antiarrhythmic peptide ZP123 on epicardial activation and repolarization pattern. Cell Commun Adhes. 2003;10:371-378. (Pubitemid 38081400)
40. Shiroshita-Takeshita A, Sakabe M, Haugan K, Hennan JK, Nattel S. Model-dependent effects of the gap junction conduction-enhancing antiarrhytmic peptide rotigaptide (ZP123) on experimental atrial fibrillation in dogs. Circulation. 2007;115:310-318. (Pubitemid 46151658)
41. Weng S, Lauven M, Schaefer T, Polontchouk L, Grover R, Dhein S. Pharmacological modification of gap junction coupling by an antiarrhythmic peptide via protein kinase C activation. FASEB J. 2002;16: 1114-1116.
42. Lin X, Zemlin C, Hennan JK, Petersen JS, Veenstra RD. Enhancement of ventricular gap-junction coupling by Rotigaptide. Cardiovasc Res. 2008; 79:416-426.
43. Wiegerinck RF, de Bakker JMT, Opthof T, de Jonge N, Kirkels H, Wilms-Schopman FJG, Coronel R. The effect of enhanced gap junctional conductance on ventricular conduction in explanted hearts from patients with heart failure. Bas Res Cardiol. 2009;104:321-332.