Extracellular sodium and potassium levels modulate cardiac conduction in mice heterozygous null for the Connexin43 gene

Pflugers Archiv European Journal of Physiology

Volumn 467, Issue 11, 2015, Pages 2287-2297

  George, Sharon A ^a,e   Sciuto, Katherine J ^b   Lin, Joyce ^c   Salama, Mohamed E ^d   Keener, James P ^b   Gourdie, Robert G ^a,e   Poelzing, Steven ^a,e  

^a Virginia Polytechnic Institute and State University   (United States)

^b UNIVERSITY OF UTAH   (United States)

^c CALIFORNIA POLYTECHNIC STATE UNIVERSITY   (United States)

^d ARUP LABORATORIES   (United States)

^e VIRGINIA TECH CARILION SCHOOL OF MEDICINE   (United States)

Author keywords

Conduction; Connexin43; Edema; Potassium; Sodium

Indexed keywords

CONNEXIN 43; POTASSIUM; SODIUM; VOLTAGE GATED SODIUM CHANNEL; GAP JUNCTION PROTEIN; GJA1 PROTEIN, MOUSE;

ADULT; ANALYTICAL PARAMETERS; ANIMAL CELL; ANIMAL TISSUE; ARTICLE; CARDIAC CONDUCTION VELOCITY; COMPARATIVE STUDY; CONTROLLED STUDY; EPICARDIUM MAPPING; GAP JUNCTION; HEART CONDUCTION; HEART MUSCLE CELL; HEART PERFUSION; HETEROZYGOSITY; ISOLATED HEART; MOUSE; NONHUMAN; OSMOLARITY; PERFUSION PRESSURE; POTASSIUM CELL LEVEL; PRIORITY JOURNAL; REGULATORY MECHANISM; SODIUM CELL LEVEL; ANIMAL; CARDIAC MUSCLE; DRUG EFFECTS; GENETICS; HEART MUSCLE CONDUCTION SYSTEM; HETEROZYGOTE; IN VITRO STUDY; KNOCKOUT MOUSE; METABOLISM; PHYSIOLOGY;

ANIMALS; CONNEXIN 43; CONNEXINS; GAP JUNCTIONS; HEART CONDUCTION SYSTEM; HETEROZYGOTE; IN VITRO TECHNIQUES; MICE; MICE, KNOCKOUT; MYOCARDIUM; POTASSIUM; SODIUM;

EID: 84943820041     PISSN: 00316768     EISSN: 14322013     Source Type: Journal    
DOI: 10.1007/s00424-015-1698-0     Document Type: Article

References (36)

1. Agullo-Pascual E, Lin X, Leo-Macias A, Zhang M, Liang FX, Li Z, Pfenniger A, Lubkemeier I, Keegan S, Fenyo D, Willecke K, Rothenberg E, Delmar M (2014) Super-resolution imaging reveals that loss of the C-terminus of connexin43 limits microtubule plus-end capture and NaV1.5 localization at the intercalated disc. Cardiovasc Res 104(2):371–381. doi:10.1093/cvr/cvu195
2. Ballantyne F 3rd, Davis LD, Reynolds EW Jr (1975) Cellular basis for reversal of hyperkalemic electrocardiographic changes by sodium. Am J Physiol 229(4):935–940
3. Bayly PV, KenKnight BH, Rogers JM, Hillsley RE, Ideker RE, Smith WM (1998) Estimation of conduction velocity vector fields from epicardial mapping data. IEEE Trans Biomed Eng 45(5):563–571. doi:10.1109/10.641337
4. Beauchamp P, Choby C, Desplantez T, de Peyer K, Green K, Yamada KA, Weingart R, Saffitz JE, Kleber AG (2004) Electrical propagation in synthetic ventricular myocyte strands from germline connexin43 knockout mice. Circ Res 95(2):170–178. doi:10.1161/01.RES.0000134923.05174.2f
5. Cascio WE, Yang H, Muller-Borer BJ, Johnson TA (2005) Ischemia-induced arrhythmia: the role of connexins, gap junctions, and attendant changes in impulse propagation. J Electrocardiol 38(4 Suppl):55–59. doi:10.1016/j.jelectrocard.2005.06.019
6. Celes MR, Torres-Duenas D, Alves-Filho JC, Duarte DB, Cunha FQ, Rossi MA (2007) Reduction of gap and adherens junction proteins and intercalated disc structural remodeling in the hearts of mice submitted to severe cecal ligation and puncture sepsis. Crit Care Med 35(9):2176–2185
7. Chitaev NA, Troyanovsky SM (1998) Adhesive but not lateral E-cadherin complexes require calcium and catenins for their formation. J Cell Biol 142(3):837–846
8. Danik SB, Liu F, Zhang J, Suk HJ, Morley GE, Fishman GI, Gutstein DE (2004) Modulation of cardiac gap junction expression and arrhythmic susceptibility. Circ Res 95(10):1035–1041. doi:10.1161/01.RES.0000148664.33695.2a
9. Dhillon PS, Gray R, Kojodjojo P, Jabr R, Chowdhury R, Fry CH, Peters NS (2013) Relationship between gap-junctional conductance and conduction velocity in mammalian myocardium. Circ Arrhythm Electrophysiol 6(6):1208–1214. doi:10.1161/CIRCEP.113.000848
10. Eloff BC, Lerner DL, Yamada KA, Schuessler RB, Saffitz JE, Rosenbaum DS (2001) High resolution optical mapping reveals conduction slowing in connexin43 deficient mice. Cardiovasc Res 51(4):681–690
11. Ganote CE, Grinwald PM, Nayler WG (1984) 2,4-Dinitrophenol (DNP)-induced injury in calcium-free hearts. J Mol Cell Cardiol 16(6):547–557
12. Gettes LS, Reuter H (1974) Slow recovery from inactivation of inward currents in mammalian myocardial fibres. J Physiol 240(3):703–724
13. Greve G, Rotevatn S, Saetersdal T, Oksendal AN, Jynge P (1985) Ultrastructural studies of intercalated disc separations in the rat heart during the calcium paradox. Res Exp Med Z Gesamte Exp Med Einschliesslich Exp Chir 185(3):195–206
14. Guerrero PA, Schuessler RB, Davis LM, Beyer EC, Johnson CM, Yamada KA, Saffitz JE (1997) Slow ventricular conduction in mice heterozygous for a connexin43 null mutation. J Clin Invest 99(8):1991–1998. doi:10.1172/JCI119367
15. Kagiyama Y, Hill JL, Gettes LS (1982) Interaction of acidosis and increased extracellular potassium on action potential characteristics and conduction in guinea pig ventricular muscle. Circ Res 51(5):614–623
16. Kleber AG, Rudy Y (2004) Basic mechanisms of cardiac impulse propagation and associated arrhythmias. Physiol Rev 84(2):431–488. doi:10.1152/physrev.00025.2003
17. Lin J, Keener JP (2014) Microdomain effects on transverse cardiac propagation. Biophys J 106(4):925–931. doi:10.1016/j.bpj.2013.11.1117
18. Lurtz MM, Louis CF (2007) Intracellular calcium regulation of connexin43. Am J Physiol Cell Physiol 293(6):C1806–C1813. doi:10.1152/ajpcell.00630.2006
19. Morley GE, Vaidya D, Samie FH, Lo C, Delmar M, Jalife J (1999) Characterization of conduction in the ventricles of normal and heterozygous Cx43 knockout mice using optical mapping. J Cardiovasc Electrophysiol 10(10):1361–1375
20. Nygren A, Giles WR (2000) Mathematical simulation of slowing of cardiac conduction velocity by elevated extracellular. Ann Biomed Eng 28(8):951–957
21. Poelzing S, Rosenbaum DS (2004) Altered connexin43 expression produces arrhythmia substrate in heart failure. Am J Physiol Heart Circ Physiol 287(4):H1762–H1770. doi:10.1152/ajpheart.00346.2004
22. Research Animals Resources UoM (2009) Reference values for laboratory animals. Normal hematology values. www.ahc.umn.edu/rar/refvalues.html. 2013
23. Rhett JM, Ongstad EL, Jourdan J, Gourdie RG (2012) Cx43 associates with Na (v)1.5 in the cardiomyocyte perinexus. J Membr Biol 245(7):411–422. doi:10.1007/s00232-012-9465-z
24. Sato PY, Musa H, Coombs W, Guerrero-Serna G, Patino GA, Taffet SM, Isom LL, Delmar M (2009) Loss of plakophilin-2 expression leads to decreased sodium current and slower conduction velocity in cultured cardiac myocytes. Circ Res 105(6):523–526. doi:10.1161/CIRCRESAHA.109.201418
25. Seidel T, Salameh A, Dhein S (2010) A simulation study of cellular hypertrophy and connexin lateralization in cardiac tissue. Biophys J 99(9):2821–2830. doi:10.1016/j.bpj.2010.09.010
26. Spach MS, Heidlage JF, Dolber PC, Barr RC (2000) Electrophysiological effects of remodeling cardiac gap junctions and cell size: experimental and model studies of normal cardiac growth. Circ Res 86(3):302–311
27. Thomas SA, Schuessler RB, Berul CI, Beardslee MA, Beyer EC, Mendelsohn ME, Saffitz JE (1998) Disparate effects of deficient expression of connexin43 on atrial and ventricular conduction: evidence for chamber-specific molecular determinants of conduction. Circulation 97(7):686–691
28. Thomas SP, Kucera JP, Bircher-Lehmann L, Rudy Y, Saffitz JE, Kleber AG (2003) Impulse propagation in synthetic strands of neonatal cardiac myocytes with genetically reduced levels of connexin43. Circ Res 92(11):1209–1216. doi:10.1161/01.RES.0000074916.41221.EA
29. Toure A, Cabo C (2010) Effect of cell geometry on conduction velocity in a subcellular model of myocardium. IEEE Trans Biomed Eng 57(9):2107–2114. doi:10.1109/TBME.2010.2050064
30. Vaidya D, Tamaddon HS, Lo CW, Taffet SM, Delmar M, Morley GE, Jalife J (2001) Null mutation of connexin43 causes slow propagation of ventricular activation in the late stages of mouse embryonic development. Circ Res 88(11):1196–1202
31. van Rijen HV, Eckardt D, Degen J, Theis M, Ott T, Willecke K, Jongsma HJ, Opthof T, de Bakker JM (2004) Slow conduction and enhanced anisotropy increase the propensity for ventricular tachyarrhythmias in adult mice with induced deletion of connexin43. Circulation 109(8):1048–1055. doi:10.1161/01.CIR.0000117402.70689.75
32. Veeraraghavan R, Lin J, Hoeker G, Keener J, Gourdie R, Poelzing S (2015) Sodium channels in the Cx43 gap junction perinexus may constitute a cardiac ephapse: an experimental and modeling study. Pflugers Arch
33. Veeraraghavan R, Salama ME, Poelzing S (2012) Interstitial volume modulates the conduction velocity-gap junction relationship. Am J Physiol Heart Circ Physiol 302(1):H278–H286. doi:10.1152/ajpheart.00868.2011
34. Watt FM, Mattey DL, Garrod DR (1984) Calcium-induced reorganization of desmosomal components in cultured human keratinocytes. J Cell Biol 99(6):2211–2215
35. Weidmann S (1955) The effect of the cardiac membrane potential on the rapid availability of the sodium-carrying system. J Physiol 127(1):213–224
36. Yanagi N, Maruyama T, Uehata S, Wakimoto Y, Sasaki Y, Arita M (1998) Electrical and mechanical abnormalities in the heart of a schizophrenic patient with hyponatremia derived from water intoxication. J Cardiol 32(3):197–204