Microdomain–specific localization of functional ion channels in cardiomyocytes: an emerging concept of local regulation and remodelling

Biophysical Reviews

Volumn 7, Issue 1, 2015, Pages 43-62

  Balycheva, Marina ^a,b   Faggian, Giuseppe ^b   Glukhov, Alexey V ^a   Gorelik, Julia ^a  

^a NATIONAL HEART AND LUNG INSTITUTE   (United Kingdom)

^b UNIVERSITY OF VERONA   (Italy)

Author keywords

Cardiomyocyte; Caveolae; Intercalated disc; Ion channel; Scanning ion conductance microscopy; T tubule

Indexed keywords

AMPHIPHYSIN; CALCIUM CHANNEL; CONNECTIN; DESMOPLAKIN; ION CHANNEL; POTASSIUM CHANNEL; SODIUM CHANNEL;

ALTERNATIVE RNA SPLICING; ARTICLE; CALCIUM TRANSPORT; CAVEOLA; CELL SIGNALING ASSAY; CONGESTIVE CARDIOMYOPATHY; COSTAMERE; ELECTRON MICROSCOPY; GAP JUNCTION; GENE AMPLIFICATION; GENE MUTATION; HEART ATRIUM FIBRILLATION; HEART INFARCTION; HEART MUSCLE CELL; HUMAN; IMMUNOFLUORESCENCE TEST; IMMUNOHISTOCHEMISTRY; IMMUNOPRECIPITATION; LIPID RAFT; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; REGULATORY MECHANISM; TOPOGRAPHY; TRANSVERSE TUBULAR SYSTEM;

EID: 84922469457     PISSN: 18672450     EISSN: 18672469     Source Type: Journal    
DOI: 10.1007/s12551-014-0159-x     Document Type: Article

References (227)

1. Ai X, Pogwizd SM (2005) Connexin 43 downregulation and dephosphorylation in nonischemic heart failure is associated with enhanced colocalized protein phosphatase type 2A. Circ Res 96(1):54–63
2. Aimond F, Alvarez JL, Rauzier JM, Lorente P, Vassort G (1999) Ionic basis of ventricular arrhythmias in remodeled rat heart during long-term myocardial infarction. Cardiovasc Res 42(2):402–415
3. Akar FG, Spragg DD, Tunin RS, Kass DA, Tomaselli GF (2004) Mechanisms underlying conduction slowing and arrhythmogenesis in nonischemic dilated cardiomyopathy. Circ Res 95(7):717–725
4. Asimaki A, Kapoor S, Plovie E et al (2014) Identification of a new modulator of the intercalated disc in a zebrafish model of arrhythmogenic cardiomyopathy. Sci Transl Med 6(240):240ra274
5. Ayettey AS, Navaratnam V (1978) The T-tubule system in the specialized and general myocardium of the rat. J Anat 127(Pt 1):125–140
6. Balijepalli RC, Kamp TJ (2008) Caveolae, ion channels and cardiac arrhythmias. Prog Biophys Mol Biol 98(2–3):149–160
7. 2+ channels to a caveolar macromolecular signaling complex is required for beta(2)-adrenergic regulation. Proc Natl Acad Sci USA 103(19):7500–7505
8. + channels localize in cholesterol and sphingolipid enriched membranes and are modulated by membrane cholesterol. Channels (Austin) 1(4):263–272
9. Barouch LA, Harrison RW, Skaf MW et al (2002) Nitric oxide regulates the heart by spatial confinement of nitric oxide synthase isoforms. Nature 416(6878):337–339
10. + channels? Circ Res 77(2):361–369
11. + channel. J Physiol 498(Pt 3):641–648
12. Bassani JW, Bassani RA, Bers DM (1994) Relaxation in rabbit and rat cardiac cells: species-dependent differences in cellular mechanisms. J Physiol 476(2):279–293
13. Benitah JP, Kerfant BG, Vassort G, Richard S, Gomez AM (2002) Altered communication between L-type calcium channels and ryanodine receptors in heart failure. Front Biosci 7:e263–e275
14. 2+ current in ventricular cardiomyocytes. J Mol Cell Cardiol 48(1):26–36
15. 2+ channels exhibit unique regulation and functional roles in cardiomyocytes. J Mol Cell Cardiol 52(2):376–387
16. Bhargava A, O’Hara T, Sikkel MB, Lyon AR, Trayanova NA, Gorelik J (2012) Nanoscale movement of L-type calcium channels in the cardiomyocyte membrane can contribute to arrhythmia during heart failure. Circulation 126, A11953
17. Bhargava A, Lin X, Novak P et al (2013) Super-resolution scanning patch clamp reveals clustering of functional ion channels in adult ventricular myocyte. Circ Res 112(8):1112–1120
18. 2+ channel alpha1 subunit contains an endoplasmic reticulum retention signal antagonized by the beta subunit. Neuron 25(1):177–190
19. Birnbaumer L, Qin N, Olcese R et al (1998) Structures and functions of calcium channel beta subunits. J Bioenerg Biomembr 30(4):357–375
20. 2+ channels and the sarcoplasmic reticulum: alterations during cardiac remodelling. Cardiovasc Res 77(2):315–324
21. Bosch RF, Zeng X, Grammer JB, Popovic K, Mewis C, Kuhlkamp V (1999) Ionic mechanisms of electrical remodeling in human atrial fibrillation. Cardiovasc Res 44(1):121–131
22. Boulware MI, Kordasiewicz H, Mermelstein PG (2007) Caveolin proteins are essential for distinct effects of membrane estrogen receptors in neurons. J Neurosci 27(37):9941–9950
23. 2+ handling during rest in rabbit ventricular myocytes. Biophys J 106(9):1902–1909
24. Brette F, Orchard C (2003) T-tubule function in mammalian cardiac myocytes. Circ Res 92(11):1182–1192
25. 2+ release at the T-tubules and surface membrane of rat ventricular myocytes. Circ Res 95(1):e1–e7
26. 2+ uptake and release in detubulated rat ventricular myocytes. J Mol Cell Cardiol 39(5):804–812
27. Brette F, Salle L, Orchard CH (2006) Quantification of calcium entry at the T-tubules and surface membrane in rat ventricular myocytes. Biophys J 90(1):381–389
28. Bruce AF, Rothery S, Dupont E, Severs NJ (2008) Gap junction remodelling in human heart failure is associated with increased interaction of connexin43 with ZO-1. Cardiovasc Res 77(4):757–765
29. Bush EW, Hood DB, Papst PJ et al (2006) Canonical transient receptor potential channels promote cardiomyocyte hypertrophy through activation of calcineurin signaling. J Biol Chem 281(44):33487–33496
30. Butler MH, David C, Ochoa GC et al (1997) Amphiphysin II (SH3P9; BIN1), a member of the amphiphysin/Rvs family, is concentrated in the cortical cytomatrix of axon initial segments and nodes of ranvier in brain and around T tubules in skeletal muscle. J Cell Biol 137(6):1355–1367
31. Cannell MB, Kong CH (2012) Local control in cardiac E-C coupling. J Mol Cell Cardiol 52(2):298–303
32. Casini S, Tan HL, Demirayak I et al (2010) Tubulin polymerization modifies cardiac sodium channel expression and gating. Cardiovasc Res 85(4):691–700
33. Catterall WA (1992) Cellular and molecular biology of voltage-gated sodium channels. Physiol Rev 72[4 Suppl]:S15–S48
34. 2+ channels. Annu Rev Cell Dev Biol 16:521–555
35. Cavalli A, Eghbali M, Minosyan TY, Stefani E, Philipson KD (2007) Localization of sarcolemmal proteins to lipid rafts in the myocardium. Cell Calcium 42(3):313–322
36. Cerrone M, Delmar M (2014) Desmosomes and the sodium channel complex: implications for arrhythmogenic cardiomyopathy and Brugada syndrome. Trends Cardiovasc Med 24(5):184–190
37. Cerrone M, Lin X, Zhang M et al (2014) Missense mutations in plakophilin-2 cause sodium current deficit and associate with a brugada syndrome phenotype. Circulation 129(10):1092–1103
38. to currents in ventricular myocytes. Front Biosci (Elite Ed) 3:1425–1442
39. Chase A, Orchard CH (2011) Ca efflux via the sarcolemmal Ca ATPase occurs only in the T-tubules of rat ventricular myocytes. J Mol Cell Cardiol 50(1):187–193
40. 2+ channels. Biophys J 79(5):2547–2556
41. 2+ channel is required for pressure overload-induced cardiac hypertrophy in mice. Circ Res 104(4):522–530
42. 2+ channels. J Biol Chem 270(50):30036–30044
43. Chu PJ, Larsen JK, Chen CC, Best PM (2004) Distribution and relative expression levels of calcium channel beta subunits within the chambers of the rat heart. J Mol Cell Cardiol 36(3):423–434
44. Clark RB, Tremblay A, Melnyk P, Allen BG, Giles WR, Fiset C (2001) T-tubule localization of the inward-rectifier K(+) channel in mouse ventricular myocytes: a role in K(+) accumulation. J Physiol 537(Pt 3):979–992
45. Cohen SA (1996) Immunocytochemical localization of rH1 sodium channel in adult rat heart atria and ventricle. Presence in terminal intercalated disks. Circulation 94(12):3083–3086
46. Cohen AW, Hnasko R, Schubert W, Lisanti MP (2004) Role of caveolae and caveolins in health and disease. Physiol Rev 84(4):1341–1379
47. Cohen RM, Foell JD, Balijepalli RC, Shah V, Hell JW, Kamp TJ (2005) Unique modulation of L-type Ca2+ channels by short auxiliary beta1d subunit present in cardiac muscle. Am J Physiol Heart Circ Physiol 288(5):H2363–H2374
48. Collin T, Wang JJ, Nargeot J, Schwartz A (1993) Molecular cloning of three isoforms of the L-type voltage-dependent calcium channel beta subunit from normal human heart. Circ Res 72(6):1337–1344
49. Cordeiro JM, Spitzer KW, Giles WR, Ershler PE, Cannell MB, Bridge JH (2001) Location of the initiation site of calcium transients and sparks in rabbit heart Purkinje cells. J Physiol 531(Pt 2):301–314
50. Danik SB, Rosner G, Lader J, Gutstein DE, Fishman GI, Morley GE (2008) Electrical remodeling contributes to complex tachyarrhythmias in connexin43-deficient mouse hearts. FASEB J 22(4):1204–1212
51. Davare MA, Avdonin V, Hall DD et al (2001) A beta2 adrenergic receptor signaling complex assembled with the Ca2+ channel Cav1.2. Science 293(5527):98–101
52. Desplantez T, McCain ML, Beauchamp P et al (2012) Connexin43 ablation in foetal atrial myocytes decreases electrical coupling, partner connexins, and sodium current. Cardiovasc Res 94(1):58–65
53. Dhar Malhotra J, Chen C, Rivolta I et al (2001) Characterization of sodium channel alpha- and beta-subunits in rat and mouse cardiac myocytes. Circulation 103(9):1303–1310
54. Dhein S, Larsen BD, Petersen JS, Mohr FW (2003) Effects of the new antiarrhythmic peptide ZP123 on epicardial activation and repolarization pattern. Cell Commun Adhes 10(4–6):371–378
55. Dibb KM, Clarke JD, Horn MA et al (2009) Characterization of an extensive transverse tubular network in sheep atrial myocytes and its depletion in heart failure. Circ Heart Fail 2(5):482–489
56. Dobrev D, Teos LY, Lederer WJ (2009) Unique atrial myocyte Ca2+ signaling. J Mol Cell Cardiol 46(4):448–451
57. Dobrzynski H, Boyett MR, Anderson RH (2007) New insights into pacemaker activity: promoting understanding of sick sinus syndrome. Circulation 115(14):1921–1932
58. Duclohier H (2005) Neuronal sodium channels in ventricular heart cells are localized near T-tubules openings. Biochem Biophys Res Commun 334(4):1135–1140
59. Dupont E, Matsushita T, Kaba RA et al (2001) Altered connexin expression in human congestive heart failure. J Mol Cell Cardiol 33(2):359–371
60. Eldstrom J, Van Wagoner DR, Moore ED, Fedida D (2006) Localization of Kv1.5 channels in rat and canine myocyte sarcolemma. FEBS Lett 580(26):6039–6046
61. Fareh S, Benardeau A, Thibault B, Nattel S (1999) The T-type Ca(2+) channel blocker mibefradil prevents the development of a substrate for atrial fibrillation by tachycardia-induced atrial remodeling in dogs. Circulation 100(21):2191–2197
62. Fawcett DW, McNutt NS (1969) The ultrastructure of the cat myocardium. I. Ventricular papillary muscle. J Cell Biol 42(1):1–45
63. Fedorov VV, Glukhov AV, Chang R (2012) Conduction barriers and pathways of the sino-atrial pacemaker complex: their role in normal rhythm and atrial arrhythmias. Am J Physiol Heart Circ Physiol 302(9):H1773–H1783
64. Feron O, Balligand JL (2006) Caveolins and the regulation of endothelial nitric oxide synthase in the heart. Cardiovasc Res 69(4):788–797
65. Foell JD, Balijepalli RC, Delisle BP et al (2004) Molecular heterogeneity of calcium channel beta-subunits in canine and human heart: evidence for differential subcellular localization. Physiol Genomics 17(2):183–200
66. Folco EJ, Liu GX, Koren G (2004) Caveolin-3 and SAP97 form a scaffolding protein complex that regulates the voltage-gated potassium channel Kv1.5. Am J Physiol Heart Circ Physiol 287(2):H681–H690
67. Fozzard HA, Hanck DA (1996) Structure and function of voltage-dependent sodium channels: comparison of brain II and cardiac isoforms. Physiol Rev 76(3):887–926
68. Galbiati F, Engelman JA, Volonte D et al (2001) Caveolin-3 null mice show a loss of caveolae, changes in the microdomain distribution of the dystrophin-glycoprotein complex, and t-tubule abnormalities. J Biol Chem 276(24):21425–21433
69. Gao T, Puri TS, Gerhardstein BL, Chien AJ, Green RD, Hosey MM (1997) Identification and subcellular localization of the subunits of L-type calcium channels and adenylyl cyclase in cardiac myocytes. J Biol Chem 272(31):19401–19407
70. Garg V, Jiao J, Hu K (2009) Regulation of ATP-sensitive K+ channels by caveolin-enriched microdomains in cardiac myocytes. Cardiovasc Res 82(1):51–58
71. Gerhardstein BL, Puri TS, Chien AJ, Hosey MM (1999) Identification of the sites phosphorylated by cyclic AMP-dependent protein kinase on the beta 2 subunit of L-type voltage-dependent calcium channels. Biochemistry 38(32):10361–10370
72. Glukhov AV, Flagg TP, Fedorov VV, Efimov IR, Nichols CG (2010) Differential K(ATP) channel pharmacology in intact mouse heart. J Mol Cell Cardiol 48(1):152–160
73. Glukhov AV, Fedorov VV, Kalish PW et al (2012) Conduction remodeling in human end-stage nonischemic left ventricular cardiomyopathy. Circulation 125(15):1835–1847
74. Glukhov AV, Balycheva M, Schobesberger S et al (2013) Distinct distribution of functional calcium channels revealed by super-resolution scanning patch-clamp in adult rat atrial cardiomyocytes. Circulation 128: A10467
75. Glukhov AV, Balycheva M, Bhogal N et al (2014) Caveolae specific location of L-type calcium channels and their role in atrial calcium cycling. Circulation 130, A15399
76. Goebel J, Logan B, Forrest K, Mieczkowski A, Roszman TL, Wills-Karp M (2005) Atorvastatin affects interleukin-2 signaling by altering the lipid raft enrichment of the interleukin-2 receptor beta chain. J Investig Med 53(6):322–328
77. Goel M, Zuo CD, Sinkins WG, Schilling WP (2007) TRPC3 channels colocalize with Na+/Ca2+ exchanger and Na+ pump in axial component of transverse-axial tubular system of rat ventricle. Am J Physiol Heart Circ Physiol 292(2):H874–H883
78. Gomes J, Finlay M, Ahmed AK et al (2012) Electrophysiological abnormalities precede overt structural changes in arrhythmogenic right ventricular cardiomyopathy due to mutations in desmoplakin-A combined murine and human study. Eur Heart J 33(15):1942–1953
79. Grabner M, Dirksen RT, Beam KG (1998) Tagging with green fluorescent protein reveals a distinct subcellular distribution of L-type and non-L-type Ca2+ channels expressed in dysgenic myotubes. Proc Natl Acad Sci USA 95(4):1903–1908
80. Gratton JP, Bernatchez P, Sessa WC (2004) Caveolae and caveolins in the cardiovascular system. Circ Res 94(11):1408–1417
81. Gu Y, Gorelik J, Spohr HA et al (2002) High-resolution scanning patch-clamp: new insights into cell function. FASEB J 16(7):748–750
82. Guo J, Wang T, Li X et al (2012) Cell surface expression of human ether-a-go-go-related gene (hERG) channels is regulated by caveolin-3 protein via the ubiquitin ligase Nedd4-2. J Biol Chem 287(40):33132–33141
83. Guo A, Zhang X, Iyer VR et al (2014) Overexpression of junctophilin-2 does not enhance baseline function but attenuates heart failure development after cardiac stress. Proc Natl Acad Sci USA 111(33):12240–12245
84. Haase H, Pfitzmaier B, McEnery MW, Morano I (2000) Expression of Ca(2+) channel subunits during cardiac ontogeny in mice and rats: identification of fetal alpha(1C) and beta subunit isoforms. J Cell Biochem 76(4):695–703
85. Hackenbrock CR, Chazotte B, Gupte SS (1986) The random collision model and a critical assessment of diffusion and collision in mitochondrial electron transport. J Bioenerg Biomembr 18(5):331–368
86. Haddock PS, Coetzee WA, Cho E et al (1999) Subcellular [Ca2+]i gradients during excitation-contraction coupling in newborn rabbit ventricular myocytes. Circ Res 85(5):415–427
87. Hansma PK, Drake B, Marti O, Gould SA, Prater CB (1989) The scanning ion-conductance microscope. Science 243(4891):641–643
88. Harvey RD, Calaghan SC (2012) Caveolae create local signalling domains through their distinct protein content, lipid profile and morphology. J Mol Cell Cardiol 52(2):366–375
89. Haufe V, Cordeiro JM, Zimmer T et al (2005) Contribution of neuronal sodium channels to the cardiac fast sodium current INa is greater in dog heart Purkinje fibers than in ventricles. Cardiovasc Res 65(1):117–127
90. Hayashi T, Arimura T, Itoh-Satoh M et al (2004) Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy. J Am Coll Cardiol 44(11):2192–2201
91. Heinzel FR, Bito V, Biesmans L et al (2008) Remodeling of T-tubules and reduced synchrony of Ca2+ release in myocytes from chronically ischemic myocardium. Circ Res 102(3):338–346
92. Hell JW, Yokoyama CT, Wong ST, Warner C, Snutch TP, Catterall WA (1993) Differential phosphorylation of two size forms of the neuronal class C L-type calcium channel alpha 1 subunit. J Biol Chem 268(26):19451–19457
93. Hell JW, Yokoyama CT, Breeze LJ, Chavkin C, Catterall WA (1995) Phosphorylation of presynaptic and postsynaptic calcium channels by cAMP-dependent protein kinase in hippocampal neurons. EMBO J 14(13):3036–3044
94. Herman DS, Lam L, Taylor MR et al (2012) Truncations of titin causing dilated cardiomyopathy. N Engl J Med 366(7):619–628
95. Hermosilla T, Moreno C, Itfinca M et al (2011) L-type calcium channel beta subunit modulates angiotensin II responses in cardiomyocytes. Channels (Austin) 5(3):280–286
96. Hong TT, Smyth JW, Gao D et al (2010) BIN1 localizes the L-type calcium channel to cardiac T-tubules. PLoS Biol 8(2):e1000312
97. Hong M, Bao L, Kefaloyianni E et al (2012a) Heterogeneity of ATP-sensitive K+ channels in cardiac myocytes: enrichment at the intercalated disk. J Biol Chem 287(49):41258–41267
98. Hong TT, Smyth JW, Chu KY et al (2012b) BIN1 is reduced and Cav1.2 trafficking is impaired in human failing cardiomyocytes. Heart Rhythm 9(5):812–820
99. Hong T, Yang H, Zhang SS et al (2014) Cardiac BIN1 folds T-tubule membrane, controlling ion flux and limiting arrhythmia. Nat Med 20(6):624–632
100. Honjo H, Boyett MR, Kodama I, Toyama J (1996) Correlation between electrical activity and the size of rabbit sino-atrial node cells. J Physiol 496(Pt 3):795–808
101. Huang B, Qin D, Deng L, Boutjdir M, El-Sherif N (2000) Reexpression of T-type Ca2+ channel gene and current in post-infarction remodeled rat left ventricle. Cardiovasc Res 46(3):442–449
102. Hullin R, Singer-Lahat D, Freichel M et al (1992) Calcium channel beta subunit heterogeneity: functional expression of cloned cDNA from heart, aorta and brain. EMBO J 11(3):885–890
103. Hullin R, Asmus F, Ludwig A, Hersel J, Boekstegers P (1999) Subunit expression of the cardiac L-type calcium channel is differentially regulated in diastolic heart failure of the cardiac allograft. Circulation 100(2):155–163
104. Hullin R, Khan IF, Wirtz S et al (2003) Cardiac L-type calcium channel beta-subunits expressed in human heart have differential effects on single channel characteristics. J Biol Chem 278(24):21623–21630
105. Hullin R, Matthes J, von Vietinghoff S et al (2007) Increased expression of the auxiliary beta(2)-subunit of ventricular L-type Ca(2)+ channels leads to single-channel activity characteristic of heart failure. PLoS One 2(3):e292
106. Huser J, Lipsius SL, Blatter LA (1996) Calcium gradients during excitation-contraction coupling in cat atrial myocytes. J Physiol 494(Pt 3):641–651
107. Ibrahim M, Gorelik J, Yacoub MH, Terracciano CM (2011) The structure and function of cardiac t-tubules in health and disease. Proc Biol Sci 278(1719):2714–2723
108. Ibrahim M, Siedlecka U, Buyandelger B et al (2013) A critical role for Telethonin in regulating t-tubule structure and function in the mammalian heart. Hum Mol Genet 22(2):372–383
109. Insel PA, Head BP, Ostrom RS et al (2005) Caveolae and lipid rafts: G protein-coupled receptor signaling microdomains in cardiac myocytes. Ann N Y Acad Sci 1047:166–172
110. Isom LL, De Jongh KS, Catterall WA (1994) Auxiliary subunits of voltage-gated ion channels. Neuron 12(6):1183–1194
111. Jaleel N, Nakayama H, Chen X et al (2008) Ca2+ influx through T- and L-type Ca2+ channels have different effects on myocyte contractility and induce unique cardiac phenotypes. Circ Res 103(10):1109–1119
112. Jansen JA, Noorman M, Musa H et al (2012) Reduced heterogeneous expression of Cx43 results in decreased Nav1.5 expression and reduced sodium current that accounts for arrhythmia vulnerability in conditional Cx43 knockout mice. Heart Rhythm 9(4):600–607
113. Jiang Y, Huang H, Liu P et al (2014) Expression and localization of TRPC proteins in rat ventricular myocytes at various developmental stages. Cell Tissue Res 355(1):201–212
114. Kaftan E, Marks AR, Ehrlich BE (1996) Effects of rapamycin on ryanodine receptor/Ca(2+)-release channels from cardiac muscle. Circ Res 78(6):990–997
115. Kamada Y, Yamada Y, Yamakage M et al (2004) Single-channel activity of L-type Ca2+ channels reconstituted with the beta2c subunit cloned from the rat heart. Eur J Pharmacol 487(1–3):37–45
116. Kamp TJ, Hell JW (2000) Regulation of cardiac L-type calcium channels by protein kinase A and protein kinase C. Circ Res 87(12):1095–1102
117. Kamp TJ, Perez-Garcia MT, Marban E (1996) Enhancement of ionic current and charge movement by coexpression of calcium channel beta 1A subunit with alpha 1C subunit in a human embryonic kidney cell line. J Physiol 492(Pt 1):89–96
118. Kinoshita H, Kuwahara K, Takano M et al (2009) T-type Ca2+ channel blockade prevents sudden death in mice with heart failure. Circulation 120(9):743–752
119. Kirk MM, Izu LT, Chen-Izu Y et al (2003) Role of the transverse-axial tubule system in generating calcium sparks and calcium transients in rat atrial myocytes. J Physiol 547(Pt 2):441–451
120. Kitamura H, Ohnishi Y, Yoshida A et al (2002) Heterogeneous loss of connexin43 protein in nonischemic dilated cardiomyopathy with ventricular tachycardia. J Cardiovasc Electrophysiol 13(9):865–870
121. Klein G, Schroder F, Vogler D et al (2003) Increased open probability of single cardiac L-type calcium channels in patients with chronic atrial fibrillation. role of phosphatase 2A. Cardiovasc Res 59(1):37–45
122. Knoll R, Hoshijima M, Hoffman HM et al (2002) The cardiac mechanical stretch sensor machinery involves a Z disc complex that is defective in a subset of human dilated cardiomyopathy. Cell 111(7):943–955
123. Kodama I, Nikmaram MR, Boyett MR, Suzuki R, Honjo H, Owen JM (1997) Regional differences in the role of the Ca2+ and Na+ currents in pacemaker activity in the sinoatrial node. Am J Physiol 272(6 Pt 2):H2793–H2806
124. Komukai K, Brette F, Yamanushi TT, Orchard CH (2002) K(+) current distribution in rat sub-epicardial ventricular myocytes. Pflugers Arch 444(4):532–538
125. Korchev YE, Bashford CL, Milovanovic M, Vodyanoy I, Lab MJ (1997) Scanning ion conductance microscopy of living cells. Biophys J 73(2):653–658
126. Kostin S, Rieger M, Dammer S et al (2003) Gap junction remodeling and altered connexin43 expression in the failing human heart. Mol Cell Biochem 242(1–2):135–144
127. Lacerda AE, Kim HS, Ruth P et al (1991) Normalization of current kinetics by interaction between the alpha 1 and beta subunits of the skeletal muscle dihydropyridine-sensitive Ca2+ channel. Nature 352(6335):527–530
128. Lacinova L, Ludwig A, Bosse E, Flockerzi V, Hofmann F (1995) The block of the expressed L-type calcium channel is modulated by the beta 3 subunit. FEBS Lett 373(2):103–107
129. Lampe PD, Lau AF (2004) The effects of connexin phosphorylation on gap junctional communication. Int J Biochem Cell Biol 36(7):1171–1186
130. Lee E, Marcucci M, Daniell L et al (2002) Amphiphysin 2 (Bin1) and T-tubule biogenesis in muscle. Science 297(5584):1193–1196
131. Lei M, Jones SA, Liu J et al (2004) Requirement of neuronal- and cardiac-type sodium channels for murine sinoatrial node pacemaking. J Physiol 559(Pt 3):835–848
132. Lenaerts I, Bito V, Heinzel FR et al (2009) Ultrastructural and functional remodeling of the coupling between Ca2+ influx and sarcoplasmic reticulum Ca2+ release in right atrial myocytes from experimental persistent atrial fibrillation. Circ Res 105(9):876–885
133. Leonoudakis D, Mailliard W, Wingerd K, Clegg D, Vandenberg C (2001) Inward rectifier potassium channel Kir2.2 is associated with synapse-associated protein SAP97. J Cell Sci 114(Pt 5):987–998
134. Li J, Patel VV, Kostetskii I et al (2005) Cardiac-specific loss of N-cadherin leads to alteration in connexins with conduction slowing and arrhythmogenesis. Circ Res 97(5):474–481
135. Li J, Kline CF, Hund TJ, Anderson ME, Mohler PJ (2010) Ankyrin-B regulates Kir6.2 membrane expression and function in heart. J Biol Chem 285(37):28723–28730
136. Lin X, Liu N, Lu J et al (2011) Subcellular heterogeneity of sodium current properties in adult cardiac ventricular myocytes. Heart Rhythm 8(12):1923–1930
137. Lipp P, Huser J, Pott L, Niggli E (1996) Spatially non-uniform Ca2+ signals induced by the reduction of transverse tubules in citrate-loaded guinea-pig ventricular myocytes in culture. J Physiol 497(Pt 3):589–597
138. Lisanti MP, Scherer PE, Vidugiriene J et al (1994) Characterization of caveolin-rich membrane domains isolated from an endothelial-rich source: implications for human disease. J Cell Biol 126(1):111–126
139. Lockwich TP, Liu X, Singh BB, Jadlowiec J, Weiland S, Ambudkar IS (2000) Assembly of Trp1 in a signaling complex associated with caveolin-scaffolding lipid raft domains. J Biol Chem 275(16):11934–11942
140. Lohn M, Furstenau M, Sagach V et al (2000) Ignition of calcium sparks in arterial and cardiac muscle through caveolae. Circ Res 87(11):1034–1039
141. Louch WE, Bito V, Heinzel FR et al (2004) Reduced synchrony of Ca2+ release with loss of T-tubules-a comparison to Ca2+ release in human failing cardiomyocytes. Cardiovasc Res 62(1):63–73
142. Louch WE, Mork HK, Sexton J et al (2006) T-tubule disorganization and reduced synchrony of Ca2+ release in murine cardiomyocytes following myocardial infarction. J Physiol 574(Pt 2):519–533
143. Lowe JS, Palygin O, Bhasin N et al (2008) Voltage-gated Nav channel targeting in the heart requires an ankyrin-G dependent cellular pathway. J Cell Biol 180(1):173–186
144. Lyon AR, MacLeod KT, Zhang Y et al (2009) Loss of T-tubules and other changes to surface topography in ventricular myocytes from failing human and rat heart. Proc Natl Acad Sci USA 106(16):6854–6859
145. Lyon AR, Bannister ML, Collins T et al (2011) SERCA2a gene transfer decreases sarcoplasmic reticulum calcium leak and reduces ventricular arrhythmias in a model of chronic heart failure. Circ Arrhythm Electrophysiol 4(3):362–372
146. Maier SK, Westenbroek RE, Schenkman KA, Feigl EO, Scheuer T, Catterall WA (2002) An unexpected role for brain-type sodium channels in coupling of cell surface depolarization to contraction in the heart. Proc Natl Acad Sci USA 99(6):4073–4078
147. Maier SK, Westenbroek RE, Yamanushi TT et al (2003) An unexpected requirement for brain-type sodium channels for control of heart rate in the mouse sinoatrial node. Proc Natl Acad Sci USA 100(6):3507–3512
148. Maier SK, Westenbroek RE, McCormick KA, Curtis R, Scheuer T, Catterall WA (2004) Distinct subcellular localization of different sodium channel alpha and beta subunits in single ventricular myocytes from mouse heart. Circulation 109(11):1421–1427
149. Makarewich CA, Correll RN, Gao H et al (2012) A caveolae-targeted L-type Ca(2)+ channel antagonist inhibits hypertrophic signaling without reducing cardiac contractility. Circ Res 110(5):669–674
150. Makarewich CA, Zhang H, Davis J et al (2014) Transient receptor potential channels contribute to pathological structural and functional remodeling after myocardial infarction. Circ Res 115(6):567–580
151. Malhotra JD, Thyagarajan V, Chen C, Isom LL (2004) Tyrosine-phosphorylated and nonphosphorylated sodium channel beta1 subunits are differentially localized in cardiac myocytes. J Biol Chem 279(39):40748–40754
152. Markandeya YS, Fahey JM, Pluteanu F, Cribbs LL, Balijepalli RC (2011) Caveolin-3 regulates protein kinase A modulation of the Ca(V)3.2 (alpha1H) T-type Ca2+ channels. J Biol Chem 286(4):2433–2444
153. Markandeya YS, Feng L, Vaidyanathan R et al (2013) Caveolin-3 regulates cardiac repolarization by integrated regulation of multiple ionic currents. Circulation 128:A15009
154. Mays DJ, Foose JM, Philipson LH, Tamkun MM (1995) Localization of the Kv1.5 K+ channel protein in explanted cardiac tissue. J Clin Invest 96(1):282–292
155. Mikami A, Imoto K, Tanabe T et al (1989) Primary structure and functional expression of the cardiac dihydropyridine-sensitive calcium channel. Nature 340(6230):230–233
156. Mitterdorfer J, Froschmayr M, Grabner M, Striessnig J, Glossmann H (1994) Calcium channels: the beta-subunit increases the affinity of dihydropyridine and Ca2+ binding sites of the alpha 1-subunit. FEBS Lett 352(2):141–145
157. Muller A, Schaefer T, Linke W et al (1997) Actions of the antiarrhythmic peptide AAP10 on intercellular coupling. Naunyn Schmiedebergs Arch Pharmacol 356(1):76–82
158. Nakamura H, Kurokawa J, Bai CX et al (2007) Progesterone regulates cardiac repolarization through a nongenomic pathway: an in vitro patch-clamp and computational modeling study. Circulation 116(25):2913–2922
159. Nakayama H, Wilkin BJ, Bodi I, Molkentin JD (2006) Calcineurin-dependent cardiomyopathy is activated by TRPC in the adult mouse heart. FASEB J 20(10):1660–1670
160. Nakayama H, Bodi I, Correll RN et al (2009) alpha1G-dependent T-type Ca2+ current antagonizes cardiac hypertrophy through a NOS3-dependent mechanism in mice. J Clin Invest 119(12):3787–3796
161. Nattel S, Maguy A, Le Bouter S, Yeh YH (2007) Arrhythmogenic ion-channel remodeling in the heart: heart failure, myocardial infarction, and atrial fibrillation. Physiol Rev 87(2):425–456
162. Nerbonne JM, Kass RS (2005) Molecular physiology of cardiac repolarization. Physiol Rev 85(4):1205–1253
163. Nikolaev VO, Moshkov A, Lyon AR et al (2010) Beta2-adrenergic receptor redistribution in heart failure changes cAMP compartmentation. Science 327(5973):1653–1657
164. Niwa N, Yasui K, Opthof T et al (2004) Cav3.2 subunit underlies the functional T-type Ca2+ channel in murine hearts during the embryonic period. Am J Physiol Heart Circ Physiol 286(6):H2257–H2263
165. Novak P, Li C, Shevchuk AI et al (2009) Nanoscale live-cell imaging using hopping probe ion conductance microscopy. Nat Methods 6(4):279–281
166. Novak P, Gorelik J, Vivekananda U et al (2013) Nanoscale-targeted patch-clamp recordings of functional presynaptic ion channels. Neuron 79(6):1067–1077
167. O’Connell KM, Whitesell JD, Tamkun MM (2008) Localization and mobility of the delayed-rectifer K+ channel Kv2.1 in adult cardiomyocytes. Am J Physiol Heart Circ Physiol 294(1):H229–H237
168. Pani B, Singh BB (2009) Lipid rafts/caveolae as microdomains of calcium signaling. Cell Calcium 45(6):625–633
169. Parton RG, Way M, Zorzi N, Stang E (1997) Caveolin-3 associates with developing T-tubules during muscle differentiation. J Cell Biol 136(1):137–154
170. Peivandi AA, Huhn A, Lehr HA et al (2005) Upregulation of phospholipase d expression and activation in ventricular pressure-overload hypertrophy. J Pharmacol Sci 98(3):244–254
171. Perez-Reyes E, Castellano A, Kim HS et al (1992) Cloning and expression of a cardiac/brain beta subunit of the L-type calcium channel. J Biol Chem 267(3):1792–1797
172. Petitprez S, Zmoos AF, Ogrodnik J et al (2011) SAP97 and dystrophin macromolecular complexes determine two pools of cardiac sodium channels Nav1.5 in cardiomyocytes. Circ Res 108(3):294–304
173. Poelzing S, Rosenbaum DS (2004) Altered connexin43 expression produces arrhythmia substrate in heart failure. Am J Physiol Heart Circ Physiol 287(4):H1762–H1770
174. Radwanski P, Brunello L, Priori SG et al (2012) Local Na+/Ca2+ signaling contributes to the propensity for arrhythmogenic spontanous Ca2+ waves during catecholaminergic polymorphic ventricular tachycardia (CPVT). Circulation 126:A17691
175. Ratajczak P, Damy T, Heymes C et al (2003) Caveolin-1 and -3 dissociations from caveolae to cytosol in the heart during aging and after myocardial infarction in rat. Cardiovasc Res 57(2):358–369
176. Razani B, Woodman SE, Lisanti MP (2002) Caveolae: from cell biology to animal physiology. Pharmacol Rev 54(3):431–467
177. Reynolds JO, Chiang DY, Wang W et al (2013) Junctophilin-2 is necessary for T-tubule maturation during mouse heart development. Cardiovasc Res 100(1):44–53
178. Rheinlaender JS, Tilman E (2009) Image formation, resolution, and height measurement in scanning ion conductance microscopy. J Appl Phys 105(9):094905 24
179. Richards MA, Clarke JD, Saravanan P et al (2011) Transverse tubules are a common feature in large mammalian atrial myocytes including human. Am J Physiol Heart Circ Physiol 301(5):H1996–H2005
180. Rickert DE, Fischer LJ (1975) Cyproheptadine and beta cell function in the rat: insulin secretion from pancreas segments in vitro. Proc Soc Exp Biol Med 150(1):1–6
181. Rizzo S, Lodder EM, Verkerk AO et al (2012) Intercalated disc abnormalities, reduced Na(+) current density, and conduction slowing in desmoglein-2 mutant mice prior to cardiomyopathic changes. Cardiovasc Res 95(4):409–418
182. Sanchez-Alonso JL, Bhogal N, Glukhov AV, Punjabi PP, Gorelik J (2014) Microdomain specific modulation of single L-type calcium channels revealed by super-resolution scanning patch-clamp in human failing cardiomyocytes. Heart Rhythm. http://ondemand.hrsonline.org/common/presentation-detail.aspx/15/23/1387/9549
183. Santos PE, Barcellos LC, Mill JG, Masuda MO (1995) Ventricular action potential and L-type calcium channel in infarct-induced hypertrophy in rats. J Cardiovasc Electrophysiol 6(11):1004–1014
184. Sato PY, Musa H, Coombs W et al (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
185. Sato PY, Coombs W, Lin X et al (2011) Interactions between ankyrin-G, Plakophilin-2, and Connexin43 at the cardiac intercalated disc. Circ Res 109(2):193–201
186. Saucerman JJ, Greenwald EC, Polanowska-Grabowska R (2014) Mechanisms of cyclic AMP compartmentation revealed by computational models. J Gen Physiol 143(1):39–48
187. Schaper J, Kostin S, Hein S, Elsasser A, Arnon E, Zimmermann R (2002) Structural remodelling in heart failure. Exp Clin Cardiol 7(2–3):64–68
188. Schulson MN, Scriven DR, Fletcher P, Moore ED (2011) Couplons in rat atria form distinct subgroups defined by their molecular partners. J Cell Sci 124(Pt 7):1167–1174
189. Scriven DR, Dan P, Moore ED (2000) Distribution of proteins implicated in excitation-contraction coupling in rat ventricular myocytes. Biophys J 79(5):2682–2691
190. Scriven DR, Asghari P, Moore ED (2013) Microarchitecture of the dyad. Cardiovasc Res 98(2):169–176
191. Severs NJ (2000) The cardiac muscle cell. Bioessays 22(2):188–199
192. Shaw RM, Fay AJ, Puthenveedu MA, von Zastrow M, Jan YN, Jan LY (2007) Microtubule plus-end-tracking proteins target gap junctions directly from the cell interior to adherens junctions. Cell 128(3):547–560
193. Shevchuk AI, Frolenkov GI, Sanchez D et al (2006) Imaging proteins in membranes of living cells by high-resolution scanning ion conductance microscopy. Angew Chem Int Ed Engl 45(14):2212–2216
194. Shibata EF, Brown TL, Washburn ZW, Bai J, Revak TJ, Butters CA (2006) Autonomic regulation of voltage-gated cardiac ion channels. J Cardiovasc Electrophysiol 17[Suppl 1]:S34–S42
195. Singer D, Biel M, Lotan I, Flockerzi V, Hofmann F, Dascal N (1991) The roles of the subunits in the function of the calcium channel. Science 253(5027):1553–1557
196. Sipido KR, Cheng H (2013) T-tubules and ryanodine receptor microdomains: on the road to translation. Cardiovasc Res 98(2):159–161
197. Sipido KR, Carmeliet E, Van de Werf F (1998) T-type Ca2+ current as a trigger for Ca2+ release from the sarcoplasmic reticulum in guinea-pig ventricular myocytes. J Physiol 508(Pt 2):439–451
198. Sipido KR, Acsai K, Antoons G, Bito V, Macquaide N (2013) T-tubule remodelling and ryanodine receptor organization modulate sodium-calcium exchange. Adv Exp Med Biol 961:375–383
199. Smyrnias I, Mair W, Harzheim D, Walker SA, Roderick HL, Bootman MD (2010) Comparison of the T-tubule system in adult rat ventricular and atrial myocytes, and its role in excitation-contraction coupling and inotropic stimulation. Cell Calcium 47(3):210–223
200. Smyth JW, Hong TT, Gao D et al (2010) Limited forward trafficking of connexin 43 reduces cell-cell coupling in stressed human and mouse myocardium. J Clin Invest 120(1):266–279
201. Song KS, Scherer PE, Tang Z et al (1996) Expression of caveolin-3 in skeletal, cardiac, and smooth muscle cells. Caveolin-3 is a component of the sarcolemma and co-fractionates with dystrophin and dystrophin-associated glycoproteins. J Biol Chem 271(25):15160–15165
202. Song LS, Pi Y, Kim SJ et al (2005) Paradoxical cellular Ca2+ signaling in severe but compensated canine left ventricular hypertrophy. Circ Res 97(5):457–464
203. Song LS, Sobie EA, McCulle S, Lederer WJ, Balke CW, Cheng H (2006) Orphaned ryanodine receptors in the failing heart. Proc Natl Acad Sci USA 103(11):4305–4310
204. Spach MS, Miller WT 3rd, Geselowitz DB, Barr RC, Kootsey JM, Johnson EA (1981) The discontinuous nature of propagation in normal canine cardiac muscle. Evidence for recurrent discontinuities of intracellular resistance that affect the membrane currents. Circ Res 48(1):39–54
205. Stangherlin A, Zaccolo M (2012) Phosphodiesterases and subcellular compartmentalized cAMP signaling in the cardiovascular system. Am J Physiol Heart Circ Physiol 302(2):H379–H390
206. Takeuchi S, Takagishi Y, Yasui K, Murata Y, Toyama J, Kodama I (2000) Voltage-gated K(+)Channel, Kv4.2, localizes predominantly to the transverse-axial tubular system of the rat myocyte. J Mol Cell Cardiol 32(7):1361–1369
207. Thomas MJ, Sjaastad I, Andersen K et al (2003) Localization and function of the Na+/Ca2+−exchanger in normal and detubulated rat cardiomyocytes. J Mol Cell Cardiol 35(11):1325–1337
208. Trafford AW, Clarke JD, Richards MA, Eisner DA, Dibb KM (2013) Calcium signalling microdomains and the t-tubular system in atrial mycoytes: potential roles in cardiac disease and arrhythmias. Cardiovasc Res 98(2):192–203
209. Vaidyanathan R, Vega AL, Song C et al (2013) The interaction of caveolin 3 protein with the potassium inward rectifier channel Kir2.1: physiology and pathology related to long qt syndrome 9 (LQT9). J Biol Chem 288(24):17472–17480
210. van Veen TA, van Rijen HV, Jongsma HJ (2006) Physiology of cardiovascular gap junctions. Adv Cardiol 42:18–40
211. Vatta M, Ackerman MJ, Ye B et al (2006) Mutant caveolin-3 induces persistent late sodium current and is associated with long-QT syndrome. Circulation 114(20):2104–2112
212. Wang YG, Dedkova EN, Ji X, Blatter LA, Lipsius SL (2005) Phenylephrine acts via IP3-dependent intracellular NO release to stimulate L-type Ca2+ current in cat atrial myocytes. J Physiol 567(Pt 1):143–157
213. Warrier S, Ramamurthy G, Eckert RL, Nikolaev VO, Lohse MJ, Harvey RD (2007) cAMP microdomains and L-type Ca2+ channel regulation in guinea-pig ventricular myocytes. J Physiol 580(Pt.3):765–776
214. Wei CJ, Francis R, Xu X, Lo CW (2005) Connexin43 associated with an N-cadherin-containing multiprotein complex is required for gap junction formation in NIH3T3 cells. J Biol Chem 280(20):19925–19936
215. Wei S, Guo A, Chen B et al (2010) T-tubule remodeling during transition from hypertrophy to heart failure. Circ Res 107(4):520–531
216. Wiegerinck RF, de Bakker JM, Opthof T et al (2009) The effect of enhanced gap junctional conductance on ventricular conduction in explanted hearts from patients with heart failure. Basic Res Cardiol 104(3):321–332
217. Willoughby D, Cooper DM (2007) Organization and Ca2+ regulation of adenylyl cyclases in cAMP microdomains. Physiol Rev 87(3):965–1010
218. Winslow RL, Greenstein JL (2011) Cardiac myocytes and local signaling in nano-domains. Prog Biophys Mol Biol 107(1):48–59
219. Woo SH, Cleemann L, Morad M (2003) Spatiotemporal characteristics of junctional and nonjunctional focal Ca2+ release in rat atrial myocytes. Circ Res 92(1):e1–e11
220. Wu X, Eder P, Chang B, Molkentin JD (2010) TRPC channels are necessary mediators of pathologic cardiac hypertrophy. Proc Natl Acad Sci USA 107(15):7000–7005
221. Yamada Y, Nagashima M, Tsutsuura M et al (2001) Cloning of a functional splice variant of L-type calcium channel beta 2 subunit from rat heart. J Biol Chem 276(50):47163–47170
222. Zaccolo M, Pozzan T (2002) Discrete microdomains with high concentration of cAMP in stimulated rat neonatal cardiac myocytes. Science 295(5560):1711–1715
223. Zhang P, Mende U (2011) Regulators of G-protein signaling in the heart and their potential as therapeutic targets. Circ Res 109(3):320–333
224. Zhang XQ, Moore RL, Tillotson DL, Cheung JY (1995) Calcium currents in postinfarction rat cardiac myocytes. Am J Physiol 269(6 Pt 1):C1464–C1473
225. Zhang C, Chen B, Guo A et al (2014) Microtubule-mediated defects in junctophilin-2 trafficking contribute to myocyte transverse-tubule remodeling and Ca2+ handling dysfunction in heart failure. Circulation 129(17):1742–1750
226. Zhou Z, January CT (1998) Both T- and L-type Ca2+ channels can contribute to excitation-contraction coupling in cardiac Purkinje cells. Biophys J 74(4):1830–1839
227. Zingman LV, Alekseev AE, Hodgson-Zingman DM, Terzic A (2007) ATP-sensitive potassium channels: metabolic sensing and cardioprotection. J Appl Physiol 103(5):1888–1893