Skip to main content
SpringerLink
Log in

Caveolae and Arrhythmogenesis

  • Chapter
  • First Online:
Electrical Diseases of the Heart

  • 3054 Accesses

Abstract

Caveolae are flask-shaped invaginations of the plasma membrane measuring approximately 50–100 nm in diameter. Caveolae are particularly rich in cholesterol and glycosphingolipids, and they are involved in a wide variety of biological processes such as membrane endocytosis, cholesterol homeostasis, tumorigenesis and cellular signaling. In the last several years, these microdomains, greatly abundant in the cardiovascular system and in particular the myocardium, were investigated for their capacity to concentrate and compartmentalize various signaling molecules such as adrenergic receptors, which have been also involved in the modulation of ion channels function. In addition, various ion channels were identified have been found to clustered to caveolae or been physically linked to caveolins, the major determinants of caveolae. Nevertheless, the relationship between the metabolism of caveolae and the ion channels function remains poorly understood. However, recent advances in the molecular genetics of caveolins revealed a tight connection between these microdomains and the susceptibility to arrhythmogenesis in humans suggesting an increasingly important role of these plasmalemmal organelles in trafficking and regulation of ion channel function.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Palade GE. An electron microscope study of the mitochondrial structure. J Histochem Cytochem. 1953;1(4):188–211.

    Article  PubMed  CAS  Google Scholar 

  2. Yamada E. The fine structure of the gall bladder epithelium of the mouse. J Biophys Biochem Cytol. 1955;1(5):445–58.

    Article  PubMed  CAS  Google Scholar 

  3. Fra AM, Williamson E, Simons K, Parton RG. De novo formation of caveolae in lymphocytes by expression of VIP21-caveolin. Proc Natl Acad Sci USA. 1995;92(19):8655–9.

    Article  PubMed  CAS  Google Scholar 

  4. Gorodinsky A, Harris DA. Glycolipid-anchored proteins in neuroblastoma cells form detergent-resistant complexes without caveolin. J Cell Biol. 1995;129(3):619–27.

    Article  PubMed  CAS  Google Scholar 

  5. Mirre C, Monlauzeur L, Garcia M, Delgrossi MH, Le Bivic A. Detergent-resistant membrane microdomains from Caco-2 cells do not contain caveolin. Am J Physiol. 1996;271(3 Pt 1):C887–94.

    PubMed  CAS  Google Scholar 

  6. Cohen AW, Hnasko R, Schubert W, Lisanti MP. Role of caveolae and caveolins in health and disease. Physiol Rev. 2004;84(4):1341–79.

    Article  PubMed  CAS  Google Scholar 

  7. Simionescu M, Simionescu N, Palade GE. Morphometric data on the endothelium of blood capillaries. J Cell Biol. 1974;60(1):128–52.

    Article  PubMed  CAS  Google Scholar 

  8. McGuire PG, Twietmeyer TA. Morphology of rapidly frozen aortic endothelial cells. Glutaraldehyde fixation increases the number of caveolae. Circ Res. 1983;53(3):424–9.

    Article  PubMed  CAS  Google Scholar 

  9. Noguchi Y, Shibata Y, Yamamoto T. Endothelial vesicular system in rapid-frozen muscle capillaries revealed by serial sectioning and deep etching. Anat Rec. 1987;217(4):355–60.

    Article  PubMed  CAS  Google Scholar 

  10. Wood MR, Wagner RC, Andrews SB, Greener DA, Williams SK. Rapidly-frozen, cultured, human endothelial cells: an ultrastructural and morphometric comparison between freshly-frozen and glutaraldehyde prefixed cells. Microcirc Endothelium Lymphatics. 1986;3(5–6):323–58.

    PubMed  Google Scholar 

  11. Fan JY, Carpentier JL, van Obberghen E, Grunfeld C, Gorden P, Orci L. Morphological changes of the 3T3-L1 fibroblast plasma membrane upon differentiation to the adipocyte form. J Cell Sci. 1983;61:219–30.

    PubMed  CAS  Google Scholar 

  12. Gratton JP, Bernatchez P, Sessa WC. Caveolae and caveolins in the cardiovascular system. Circ Res. 2004;94(11):1408–17.

    Article  PubMed  CAS  Google Scholar 

  13. Ishikawa H. Formation of elaborate networks of T-system tubules in cultured skeletal muscle with special reference to the T-system formation. J Cell Biol. 1968;38(1):51–66.

    Article  PubMed  CAS  Google Scholar 

  14. Parton RG, Way M, Zorzi N, Stang E. Caveolin-3 associates with developing T-tubules during muscle differentiation. J Cell Biol. 1997;136(1):137–54.

    Article  PubMed  CAS  Google Scholar 

  15. Gabella G, Blundell D. Effect of stretch and contraction on caveolae of smooth muscle cells. Cell Tissue Res. 1978;190(2):255–71.

    Article  PubMed  CAS  Google Scholar 

  16. Sawada H, Ishikawa H, Yamada E. High resolution scanning electron microscopy of frog sartorius muscle. Tissue Cell. 1978;10(1):179–90.

    Article  PubMed  CAS  Google Scholar 

  17. Frank JS, Beydler S, Kreman M, Rau EE. Structure of the freeze-fractured sarcolemma in the normal and anoxic rabbit myocardium. Circ Res. 1980;47(1):131–43.

    Article  PubMed  CAS  Google Scholar 

  18. Severs NJ. Plasma membrane cholesterol in myocardial muscle and capillary endothelial cells. Distribution of filipin-induced deformations in freeze-fracture. Eur J Cell Biol. 1981;25(2):289–99.

    PubMed  CAS  Google Scholar 

  19. Izumi T, Shibata Y, Yamamoto T. Striped structures on the cytoplasmic surface membranes of the endothelial vesicles of the rat aorta revealed by quick-freeze, deep-etching replicas. Anat Rec. 1988;220(3):225–32.

    Article  PubMed  CAS  Google Scholar 

  20. Fujimoto T. Cell biology of caveolae and its implication for clinical medicine. Nagoya J Med Sci. 2000;63(1–2):9–18.

    PubMed  CAS  Google Scholar 

  21. Isshiki M, Ando J, Korenaga R, et al. Endothelial Ca2+ waves preferentially originate at specific loci in caveolin-rich cell edges. Proc Natl Acad Sci USA. 1998;95(9):5009–14.

    Article  PubMed  CAS  Google Scholar 

  22. Isshiki M, Ando J, Yamamoto K, Fujita T, Ying Y, Anderson RG. Sites of Ca(2+) wave initiation move with caveolae to the trailing edge of migrating cells. J Cell Sci. 2002;115(Pt 3):475–84.

    PubMed  CAS  Google Scholar 

  23. Parat MO, Anand-Apte B, Fox PL. Differential caveolin-1 polarization in endothelial cells during migration in two and three dimensions. Mol Biol Cell. 2003;14(8):3156–68.

    Article  PubMed  CAS  Google Scholar 

  24. Anderson RG. The caveolae membrane system. Annu Rev Biochem. 1998;67:199–225.

    Article  PubMed  CAS  Google Scholar 

  25. Edidin M. The state of lipid rafts: from model membranes to cells. Annu Rev Biophys Biomol Struct. 2003;32:257–83.

    Article  PubMed  CAS  Google Scholar 

  26. Rothberg KG, Heuser JE, Donzell WC, Ying YS, Glenney JR, Anderson RG. Caveolin, a protein component of caveolae membrane coats. Cell. 1992;68(4):673–82.

    Article  PubMed  CAS  Google Scholar 

  27. Glenney Jr JR, Kindy MS, Zokas L. Isolation of a new member of the S100 protein family: amino acid sequence, tissue, and subcellular distribution. J Cell Biol. 1989;108(2):569–78.

    Article  PubMed  CAS  Google Scholar 

  28. Glenney Jr JR. Tyrosine phosphorylation of a 22-kDa protein is correlated with transformation by Rous sarcoma virus. J Biol Chem. 1989;264(34):20163–6.

    PubMed  CAS  Google Scholar 

  29. Kurzchalia TV, Dupree P, Parton RG, et al. VIP21, a 21-kD membrane protein is an integral component of trans-Golgi-network-derived transport vesicles. J Cell Biol. 1992;118(5):1003–14.

    Article  PubMed  CAS  Google Scholar 

  30. Scherer PE, Okamoto T, Chun M, Nishimoto I, Lodish HF, Lisanti MP. Identification, sequence, and expression of caveolin-2 defines a caveolin gene family. Proc Natl Acad Sci USA. 1996;93(1):131–5.

    Article  PubMed  CAS  Google Scholar 

  31. Tang Z, Scherer PE, Okamoto T, et al. Molecular cloning of caveolin-3, a novel member of the caveolin gene family expressed predominantly in muscle. J Biol Chem. 1996;271(4):2255–61.

    Article  PubMed  CAS  Google Scholar 

  32. Stan RV. Structure of caveolae. Biochim Biophys Acta. 2005;1746(3):334–48.

    Article  PubMed  CAS  Google Scholar 

  33. Volonte D, Liu Y, Galbiati F. The modulation of caveolin-1 expression controls satellite cell activation during muscle repair. FASEB J. 2005;19(2):237–9.

    PubMed  CAS  Google Scholar 

  34. Rahman A, Swärd K. The role of caveolin-1 in cardiovascular regulation. Acta Physiol (Oxf). 2009;195(2):231–45.

    Article  CAS  Google Scholar 

  35. Volonte D, McTiernan CF, Drab M, Kasper M, Galbiati F. Caveolin-1 and caveolin-3 form ­heterooligomeric complexes in atrial cardiac myocytes that are required for doxorubicin-induced apoptosis. Am J Physiol Heart Circ Physiol. 2008;294(1):H392–401.

    Article  PubMed  CAS  Google Scholar 

  36. Li S, Song KS, Koh SS, Kikuchi A, Lisanti MP. Baculovirus-based expression of mammalian caveolin in Sf21 insect cells. A model system for the biochemical and morphological study of caveolae biogenesis. J Biol Chem. 1996;271(45):28647–54.

    Article  PubMed  CAS  Google Scholar 

  37. Scherer PE, Tang Z, Chun M, Sargiacomo M, Lodish HF, Lisanti MP. Caveolin isoforms differ in their N-terminal protein sequence and subcellular distribution. Identification and epitope mapping of an isoform-specific monoclonal antibody probe. J Biol Chem. 1995;270(27):16395–401.

    Article  PubMed  CAS  Google Scholar 

  38. Way M, Parton RG. M-caveolin, a muscle-specific caveolin-related protein. FEBS Lett. 1995;376(1–2):108–12.

    Article  PubMed  CAS  Google Scholar 

  39. Song KS, Scherer PE, Tang Z, et al. 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. 1996;271(25):15160–5.

    Article  PubMed  CAS  Google Scholar 

  40. Galbiati F, Volonte D, Engelman JA, Scherer PE, Lisanti MP. Targeted down-regulation of caveolin-3 is sufficient to inhibit myotube formation in differentiating C2C12 myoblasts. Transient activation of p38 mitogen-activated protein kinase is required for induction of caveolin-3 expression and subsequent myotube formation. J Biol Chem. 1999;274(42):30315–21.

    Article  PubMed  CAS  Google Scholar 

  41. Ahn AH, Yoshida M, Anderson MS, et al. Cloning of human basic A1, a distinct 59-kDa dystrophin-associated protein encoded on chromosome 8q23-24. Proc Natl Acad Sci USA. 1994;91(10):4446–50.

    Article  PubMed  CAS  Google Scholar 

  42. Adams ME, Dwyer TM, Dowler LL, White RA, Froehner SC. Mouse alpha 1- and beta 2-syntrophin gene structure, chromosome localization, and homology with a discs large domain. J Biol Chem. 1995;270(43):25859–65.

    Article  PubMed  CAS  Google Scholar 

  43. Piluso G, Mirabella M, Ricci E, et al. Gamma1- and gamma2-syntrophins, two novel dystrophin-binding proteins localized in neuronal cells. J Biol Chem. 2000;275(21):15851–60.

    Article  PubMed  CAS  Google Scholar 

  44. Sotgia F, Lee JK, Das K, et al. Caveolin-3 directly interacts with the C-terminal tail of beta -dystroglycan. Identification of a central WW-like domain within caveolin family members. J Biol Chem. 2000;275(48):38048–58.

    Article  PubMed  CAS  Google Scholar 

  45. Bonilla E, Fischbeck K, Schotland DL. Freeze-fracture studies of muscle caveolae in human muscular dystrophy. Am J Pathol. 1981;104(2):167–73.

    PubMed  CAS  Google Scholar 

  46. Repetto S, Bado M, Broda P, et al. Increased ­number of caveolae and caveolin-3 overexpression in Duchenne muscular dystrophy. Biochem Biophys Res Commun. 1999;261(3):547–50.

    Article  PubMed  CAS  Google Scholar 

  47. Vaghy PL, Fang J, Wu W, Vaghy LP. Increased caveolin-3 levels in mdx mouse muscles. FEBS Lett. 1998;431(1):125–7.

    Article  PubMed  CAS  Google Scholar 

  48. Drab M, Verkade P, Elger M, et al. Loss of caveolae, vascular dysfunction, and pulmonary defects in caveolin-1 gene-disrupted mice. Science. 2001;293(5539):2449–52.

    Article  PubMed  CAS  Google Scholar 

  49. Razani B, Engelman JA, Wang XB, et al. Caveolin-1 null mice are viable but show evidence of hyperproliferative and vascular abnormalities. J Biol Chem. 2001;276(41):38121–38.

    PubMed  CAS  Google Scholar 

  50. Zhao YY, Liu Y, Stan RV, et al. Defects in caveolin-1 cause dilated cardiomyopathy and pulmonary hypertension in knockout mice. Proc Natl Acad Sci USA. 2002;99(17):11375–80.

    Article  PubMed  CAS  Google Scholar 

  51. Park DS, Cohen AW, Frank PG, et al. Caveolin-1 null (-/-) mice show dramatic reductions in life span. Biochemistry. 2003;42(51):15124–31.

    Article  PubMed  CAS  Google Scholar 

  52. Cohen AW, Park DS, Woodman SE, Williams TM, Chandra M, Shirani J, et al. Caveolin-1 null mice develop cardiac hypertrophy with hyperactivation of p42/44 MAP kinase in cardiac fibroblasts. Am J Physiol Cell Physiol. 2003;284(2):C457–74.

    PubMed  CAS  Google Scholar 

  53. Miyasato SK, Loeffler J, Shohet R, Zhang J, Lindsey M, Le Saux CJ. Caveolin-1 modulates TGF-β1 signaling in cardiac remodeling. Matrix Biol. 2011;30(5–6):318–29.

    Article  PubMed  CAS  Google Scholar 

  54. Galbiati F, Engelman JA, Volonte D, et al. 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. 2001;276(24):21425–33.

    Article  PubMed  CAS  Google Scholar 

  55. Hagiwara Y, Sasaoka T, Araishi K, et al. Caveolin-3 deficiency causes muscle degeneration in mice. Hum Mol Genet. 2000;9(20):3047–54.

    Article  PubMed  CAS  Google Scholar 

  56. Woodman SE, Park DS, Cohen AW, et al. Caveolin-3 knock-out mice develop a progressive cardiomyopathy and show hyperactivation of the p42/44 MAPK cascade. J Biol Chem. 2002;277(41):38988–97.

    Article  PubMed  CAS  Google Scholar 

  57. Hayashi T, Arimura T, Ueda K, et al. Identification and functional analysis of a caveolin-3 mutation associated with familial hypertrophic cardiomyopathy. Biochem Biophys Res Commun. 2004;313(1):178–84.

    Article  PubMed  CAS  Google Scholar 

  58. Park DS, Woodman SE, Schubert W, et al. Caveolin-1/3 double-knockout mice are viable, but lack both muscle and non-muscle caveolae, and develop a severe cardiomyopathic phenotype. Am J Pathol. 2002;160(6):2207–17.

    Article  PubMed  CAS  Google Scholar 

  59. Sargiacomo M, Scherer PE, Tang Z, et al. Oligomeric structure of caveolin: implications for caveolae membrane organization. Proc Natl Acad Sci USA. 1995;92(20):9407–11.

    Article  PubMed  CAS  Google Scholar 

  60. Schlegel A, Arvan P, Lisanti MP. Caveolin-1 binding to endoplasmic reticulum membranes and entry into the regulated secretory pathway are regulated by serine phosphorylation. Protein sorting at the level of the endoplasmic reticulum. J Biol Chem. 2001;276(6):4398–408.

    Article  PubMed  CAS  Google Scholar 

  61. Ren X, Ostermeyer AG, Ramcharan LT, Zeng Y, Lublin DM, Brown DA. Conformational defects slow Golgi exit, block oligomerization, and reduce raft affinity of caveolin-1 mutant proteins. Mol Biol Cell. 2004;15(10):4556–67.

    Article  PubMed  CAS  Google Scholar 

  62. Vogel U, Sandvig K, van Deurs B. Expression of caveolin-1 and polarized formation of invaginated caveolae in Caco-2 and MDCK II cells. J Cell Sci. 1998;111(Pt 6):825–32.

    PubMed  CAS  Google Scholar 

  63. Dietzen DJ, Hastings WR, Lublin DM. Caveolin is palmitoylated on multiple cysteine residues. Palmitoylation is not necessary for localization of caveolin to caveolae. J Biol Chem. 1995;270(12):6838–42.

    Article  PubMed  CAS  Google Scholar 

  64. Monier S, Dietzen DJ, Hastings WR, Lublin DM, Kurzchalia TV. Oligomerization of VIP21-caveolin in vitro is stabilized by long chain fatty acylation or cholesterol. FEBS Lett. 1996;388(2–3):143–9.

    Article  PubMed  CAS  Google Scholar 

  65. Parat MO, Fox PL. Palmitoylation of caveolin-1 in endothelial cells is post-translational but irreversible. J Biol Chem. 2001;276(19):15776–82.

    Article  PubMed  CAS  Google Scholar 

  66. Razani B, Woodman SE, Lisanti MP. Caveolae: from cell biology to animal physiology. Pharmacol Rev. 2002;54(3):431–67.

    Article  PubMed  CAS  Google Scholar 

  67. Dupree P, Parton RG, Raposo G, Kurzchalia TV, Simons K. Caveolae and sorting in the trans-Golgi network of epithelial cells. EMBO J. 1993;12(4):1597–605.

    PubMed  CAS  Google Scholar 

  68. Monier S, Parton RG, Vogel F, Behlke J, Henske A, Kurzchalia TV. VIP21-caveolin, a membrane protein constituent of the caveolar coat, oligomerizes in vivo and in vitro. Mol Biol Cell. 1995;6(7):911–27.

    PubMed  CAS  Google Scholar 

  69. Schlegel A, Schwab RB, Scherer PE, Lisanti MP. A role for the caveolin scaffolding domain in mediating the membrane attachment of caveolin-1. The caveolin scaffolding domain is both necessary and sufficient for membrane binding in vitro. J Biol Chem. 1999;274(32):22660–7.

    Article  PubMed  CAS  Google Scholar 

  70. Woodman SE, Schlegel A, Cohen AW, Lisanti MP. Mutational analysis identifies a short atypical membrane attachment sequence (KYWFYR) within caveolin-1. Biochemistry. 2002;41(11):3790–5.

    Article  PubMed  CAS  Google Scholar 

  71. Luetterforst R, Stang E, Zorzi N, Carozzi A, Way M, Parton RG. Molecular characterization of caveolin association with the Golgi complex: identification of a cis-Golgi targeting domain in the caveolin molecule. J Cell Biol. 1999;145(7):1443–59.

    Article  PubMed  CAS  Google Scholar 

  72. Schlegel A, Pestell RG, Lisanti MP. Caveolins in cholesterol trafficking and signal transduction: implications for human disease. Front Biosci. 2000;5:D929–37.

    Article  PubMed  CAS  Google Scholar 

  73. Song KS, Tang Z, Li S, Lisanti MP. Mutational analysis of the properties of caveolin-1. A novel role for the C-terminal domain in mediating homo-typic caveolin-caveolin interactions. J Biol Chem. 1997;272(7):4398–403.

    Article  PubMed  CAS  Google Scholar 

  74. Mora R, Bonilha VL, Marmorstein A, et al. Caveolin-2 localizes to the golgi complex but redistributes to plasma membrane, caveolae, and rafts when co-expressed with caveolin-1. J Biol Chem. 1999;274(36):25708–17.

    Article  PubMed  CAS  Google Scholar 

  75. Parolini I, Sargiacomo M, Galbiati F, et al. Expression of caveolin-1 is required for the transport of caveolin-2 to the plasma membrane. Retention of caveolin-2 at the level of the golgi complex. J Biol Chem. 1999;274(36):25718–25.

    Article  PubMed  CAS  Google Scholar 

  76. Scherer PE, Lewis RY, Volonte D, et al. Cell-type and tissue-specific expression of caveolin-2. Caveolins 1 and 2 co-localize and form a stable hetero-oligomeric complex in vivo. J Biol Chem. 1997;272(46):29337–46.

    Article  PubMed  CAS  Google Scholar 

  77. Rybin VO, Grabham PW, Elouardighi H, Steinberg SF. Caveolae-associated proteins in cardiomyocytes: caveolin-2 expression and interactions with caveolin-3. Am J Physiol Heart Circ Physiol. 2003;285(1):H325–32.

    PubMed  CAS  Google Scholar 

  78. Woodman SE, Sotgia F, Galbiati F, Minetti C, Lisanti MP. Caveolinopathies: mutations in caveolin-3 cause four distinct autosomal dominant muscle diseases. Neurology. 2004;62(4):538–43.

    Article  PubMed  CAS  Google Scholar 

  79. Bist A, Fielding PE, Fielding CJ. Two sterol regulatory element-like sequences mediate up-regulation of caveolin gene transcription in response to low density lipoprotein free cholesterol. Proc Natl Acad Sci USA. 1997;94(20):10693–8.

    Article  PubMed  CAS  Google Scholar 

  80. Fielding CJ, Bist A, Fielding PE. Caveolin mRNA levels are up-regulated by free cholesterol and down-regulated by oxysterols in fibroblast monolayers. Proc Natl Acad Sci USA. 1997;94(8):3753–8.

    Article  PubMed  CAS  Google Scholar 

  81. Smart EJ, Ying YS, Conrad PA, Anderson RG. Caveolin moves from caveolae to the Golgi apparatus in response to cholesterol oxidation. J Cell Biol. 1994;127(5):1185–97.

    Article  PubMed  CAS  Google Scholar 

  82. Graf GA, Matveev SV, Smart EJ. Class B scavenger receptors, caveolae and cholesterol homeostasis. Trends Cardiovasc Med. 1999;9(8):221–5.

    Article  PubMed  CAS  Google Scholar 

  83. Frank PG, Lisanti MP. Caveolin-1 and caveolae in atherosclerosis: differential roles in fatty streak formation and neointimal hyperplasia. Curr Opin Lipidol. 2004;15(5):523–9.

    Article  PubMed  CAS  Google Scholar 

  84. Thomsen P, Roepstorff K, Stahlhut M, van Deurs B. Caveolae are highly immobile plasma membrane microdomains, which are not involved in constitutive endocytic trafficking. Mol Biol Cell. 2002;13(1):238–50.

    Article  PubMed  CAS  Google Scholar 

  85. Pelkmans L, Helenius A. Endocytosis via caveolae. Traffic. 2002;3(5):311–20.

    Article  PubMed  CAS  Google Scholar 

  86. Lisanti MP, Scherer PE, Tang Z, Sargiacomo M. Caveolae, caveolin and caveolin-rich membrane domains: a signalling hypothesis. Trends Cell Biol. 1994;4(7):231–5.

    Article  PubMed  CAS  Google Scholar 

  87. Sargiacomo M, Sudol M, Tang Z, Lisanti MP. Signal transducing molecules and glycosyl-phosphatidylinositol-linked proteins form a caveolin-rich insoluble complex in MDCK cells. J Cell Biol. 1993;122(4):789–807.

    Article  PubMed  CAS  Google Scholar 

  88. Horikawa YT, Panneerselvam M, Kawaraguchi Y, Tsutsumi YM, Ali SS, Balijepalli RC, et al. Cardiac-specific overexpression of caveolin-3 attenuates cardiac hypertrophy and increases natriuretic peptide expression and signaling. J Am Coll Cardiol. 2011;57(22):2273–83.

    Article  PubMed  CAS  Google Scholar 

  89. Yarbrough TL, Lu T, Lee HC, Shibata EF. Localization of cardiac sodium channels in caveolin-rich membrane domains: regulation of sodium current amplitude. Circ Res. 2002;90(4):443–9.

    Article  PubMed  CAS  Google Scholar 

  90. Balijepalli RC, Foell JD, Hall DD, Hell JW, Kamp TJ. L-type Ca2+ channels are present in caveolae and associated with caveolin-3 and beta(2)-AR in ventricular myocytes. J Gen Physiol. 2004;124:31A.

    Google Scholar 

  91. Balijepalli RC, Foell JD, Hall DD, Hell JW, Kamp TJ. Localization of cardiac L-type Ca(2+) channels to a caveolar macromolecular signaling complex is required for beta(2)-adrenergic regulation. Proc Natl Acad Sci USA. 2006;103(19):7500–5.

    Article  PubMed  CAS  Google Scholar 

  92. Martens JR, Sakamoto N, Sullivan SA, Grobaski TD, Tamkun MM. Isoform-specific localization of voltage-gated K+ channels to distinct lipid raft populations. Targeting of Kv1.5 to caveolae. J Biol Chem. 2001;276(11):8409–14.

    Article  PubMed  CAS  Google Scholar 

  93. Barbuti A, Gravante B, Riolfo M, Milanesi R, Terragni B, DiFrancesco D. Localization of pacemaker channels in lipid rafts regulates channel kinetics. Circ Res. 2004;94(10):1325–31.

    Article  PubMed  CAS  Google Scholar 

  94. Bossuyt J, Taylor BE, James-Kracke M, Hale CC. The cardiac sodium-calcium exchanger associates with caveolin-3. Ann N Y Acad Sci. 2002;976:197–204.

    Article  PubMed  CAS  Google Scholar 

  95. Sampson LJ, Hayabuchi Y, Standen NB, Dart C. Caveolae localize protein kinase A signaling to arterial ATP-sensitive potassium channels. Circ Res. 2004;95(10):1012–8.

    Article  PubMed  CAS  Google Scholar 

  96. Yamamoto S, Kita S, Iyoda T, Yamada T, Ehara T, Iwamoto T. Caveolin-3 modulates the activity of the volume-regulated anion channel in mouse ventricular cells. J Physiol Sci. 2010;60:S170.

    Google Scholar 

  97. Gervásio OL, Whitehead NP, Yeung EW, Phillips WD, Allen DG. TRPC1 binds to caveolin-3 and is regulated by Src kinase - role in Duchenne muscular dystrophy. J Cell Sci. 2008;121(Pt 13):2246–55.

    Article  PubMed  CAS  Google Scholar 

  98. Martens JR, Navarro-Polanco R, Coppock EA, et al. Differential targeting of Shaker-like potassium channels to lipid rafts. J Biol Chem. 2000;275(11):7443–6.

    Article  PubMed  CAS  Google Scholar 

  99. McEwen DP, Li Q, Jackson S, Jenkins PM, Martens JR. Caveolin regulates kv1.5 trafficking to ­cholesterol-rich membrane microdomains. Mol Pharmacol. 2008;73(3):678–85.

    Article  PubMed  CAS  Google Scholar 

  100. Maruoka ND, Steele DF, Au BP, et al. Alpha-actinin-2 couples to cardiac Kv1.5 channels, regulating current density and channel localization in HEK cells. FEBS Lett. 2000;473(2):188–94.

    Article  PubMed  CAS  Google Scholar 

  101. Mays DJ, Foose JM, Philipson LH, Tamkun MM. Localization of the Kv1.5 K+ channel protein in explanted cardiac tissue. J Clin Invest. 1995;96(1):282–92.

    Article  PubMed  CAS  Google Scholar 

  102. Darby PJ, Kwan CY, Daniel EE. Caveolae from canine airway smooth muscle contain the necessary components for a role in Ca(2+) handling. Am J Physiol Lung Cell Mol Physiol. 2000;279(6):L1226–35.

    PubMed  CAS  Google Scholar 

  103. Jiang C, Atkinson D, Towbin JA, et al. Two long QT syndrome loci map to chromosomes 3 and 7 with evidence for further heterogeneity. Nat Genet. 1994;8(2):141–7.

    Article  PubMed  CAS  Google Scholar 

  104. Splawski I, Timothy KW, Sharpe LM, et al. Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism. Cell. 2004;119(1):19–31.

    Article  PubMed  CAS  Google Scholar 

  105. Splawski I, Timothy KW, Decher N, et al. Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations. Proc Natl Acad Sci USA. 2005;102(23):8089–96; discussion 6–8.

    Article  PubMed  CAS  Google Scholar 

  106. Jorgensen AO, Shen AC, Arnold W, Leung AT, Campbell KP. Subcellular distribution of the 1,4-dihydropyridine receptor in rabbit skeletal muscle in situ: an immunofluorescence and immunocolloidal gold-labeling study. J Cell Biol. 1989;109(1):135–47.

    Article  PubMed  CAS  Google Scholar 

  107. Melkonian KA, Ostermeyer AG, Chen JZ, Roth MG, Brown DA. Role of lipid modifications in targeting proteins to detergent-resistant membrane rafts. Many raft proteins are acylated, while few are prenylated. J Biol Chem. 1999;274(6):3910–7.

    Article  PubMed  CAS  Google Scholar 

  108. Perez AS, Bredt DS. The N-terminal PDZ-containing region of postsynaptic density-95 mediates ­association with caveolar-like lipid domains. Neurosci Lett. 1998;258(2):121–3.

    Article  PubMed  CAS  Google Scholar 

  109. Scannevin RH, Murakoshi H, Rhodes KJ, Trimmer JS. Identification of a cytoplasmic domain important in the polarized expression and clustering of the Kv2.1 K+ channel. J Cell Biol. 1996;135(6 Pt 1):1619–32.

    Article  PubMed  CAS  Google Scholar 

  110. Venema VJ, Ju H, Zou R, Venema RC. Interaction of neuronal nitric-oxide synthase with caveolin-3 in skeletal muscle. Identification of a novel caveolin scaffolding/inhibitory domain. J Biol Chem. 1997;272(45):28187–90.

    Article  PubMed  CAS  Google Scholar 

  111. Campbell KP, Kahl SD. Association of dystrophin and an integral membrane glycoprotein. Nature. 1989;338(6212):259–62.

    Article  PubMed  CAS  Google Scholar 

  112. Durbeej M, Campbell KP. Muscular dystrophies involving the dystrophin-glycoprotein complex: an overview of current mouse models. Curr Opin Genet Dev. 2002;12(3):349–61.

    Article  PubMed  CAS  Google Scholar 

  113. Feron O, Kelly RA. Gaining respectability: membrane-delimited, caveolar-restricted activation of ion channels. Circ Res. 2002;90(4):369–70.

    Article  PubMed  CAS  Google Scholar 

  114. Ahn AH, Kunkel LM. Syntrophin binds to an alternatively spliced exon of dystrophin. J Cell Biol. 1995;128(3):363–71.

    Article  PubMed  CAS  Google Scholar 

  115. Vatta M, Faulkner G. Cytoskeletal basis of ion channel function in cardiac muscle. Future Cardiol. 2006;2(4):467–76.

    Article  PubMed  CAS  Google Scholar 

  116. Kachinsky AM, Froehner SC, Milgram SL. A PDZ-containing scaffold related to the dystrophin complex at the basolateral membrane of epithelial cells. J Cell Biol. 1999;145(2):391–402.

    Article  PubMed  CAS  Google Scholar 

  117. Chockalingam PS, Gee SH, Jarrett HW. Pleckstrin homology domain 1 of mouse alpha 1-syntrophin binds phosphatidylinositol 4,5-bisphosphate. Biochemistry. 1999;38(17):5596–602.

    Article  PubMed  CAS  Google Scholar 

  118. Brenman JE, Chao DS, Gee SH, et al. Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and alpha1-syntrophin mediated by PDZ domains. Cell. 1996;84(5):757–67.

    Article  PubMed  CAS  Google Scholar 

  119. Frigeri A, Nicchia GP, Verbavatz JM, Valenti G, Svelto M. Expression of aquaporin-4 in fast-twitch fibers of mammalian skeletal muscle. J Clin Invest. 1998;102(4):695–703.

    Article  PubMed  CAS  Google Scholar 

  120. Hasegawa M, Cuenda A, Spillantini MG, et al. Stress-activated protein kinase-3 interacts with the PDZ domain of alpha1-syntrophin. A mechanism for specific substrate recognition. J Biol Chem. 1999;274(18):12626–31.

    Article  PubMed  CAS  Google Scholar 

  121. Gee SH, Madhavan R, Levinson SR, Caldwell JH, Sealock R, Froehner SC. Interaction of muscle and brain sodium channels with multiple members of the syntrophin family of dystrophin-associated proteins. J Neurosci. 1998;18(1):128–37.

    PubMed  CAS  Google Scholar 

  122. Adams ME, Mueller HA, Froehner SC. In vivo requirement of the alpha-syntrophin PDZ domain for the sarcolemmal localization of nNOS and aquaporin-4. J Cell Biol. 2001;155(1):113–22.

    Article  PubMed  CAS  Google Scholar 

  123. Ou Y, Strege P, Miller SM, et al. Syntrophin gamma 2 regulates SCN5A gating by a PDZ domain-mediated interaction. J Biol Chem. 2003;278(3):1915–23.

    Article  PubMed  CAS  Google Scholar 

  124. Bossuyt J, Taylor BE, James-Kracke M, Hale CC. Evidence for cardiac sodium-calcium exchanger association with caveolin-3. FEBS Lett. 2002;511(1–3):113–7.

    Article  PubMed  CAS  Google Scholar 

  125. Wu G, Ai T, Kim JJ, Mohapatra B, Xi Y, Li Z, et al. Alpha-1-syntrophin mutation and the long QT syndrome: a disease of sodium channel disruption. Circ Arrhythm Electrophysiol. 2008;1:193–201.

    Article  PubMed  CAS  Google Scholar 

  126. Ueda K, Valdivia C, Medeiros-Domingo A, Tester DJ, Vatta M, Farrugia G, et al. Syntrophin mutation associated with long QT syndrome through activation of the nNOS-SCN5A macromolecular complex. Proc Natl Acad Sci USA. 2008;105:9355–60.

    Article  PubMed  CAS  Google Scholar 

  127. Vatta M, Ackerman MJ, Ye B, Makielski J, Ughanze EE, Taylor EW, et al. Mutant caveolin-3 induces persistent late sodium current and is associated with long QT syndrome. Circulation. 2006;114(20):2104–12.

    Article  PubMed  CAS  Google Scholar 

  128. Cronk LB, Ye B, Kaku T, Tester DJ, Vatta M, Makielski JC, et al. Novel mechanism for sudden infant death syndrome: persistent late sodium current secondary to mutations in caveolin-3. Heart Rhythm. 2007;4(2):161–6.

    Article  PubMed  Google Scholar 

  129. Abriel H. Cardiac sodium channel Na(v)1.5 and interacting proteins: physiology and pathophysiology. J Mol Cell Cardiol. 2010;48(1):2–11.

    Article  PubMed  CAS  Google Scholar 

  130. Holmes TC, Fadool DA, Levitan IB. Tyrosine phosphorylation of the Kv1.3 potassium channel. J Neurosci. 1996;16(5):1581–90.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, NAB 0220, Houston, TX, 77030, USA

    Matteo Vatta PhD

Authors
  1. Matteo Vatta PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Matteo Vatta PhD .

Editor information

Editors and Affiliations

  1. , Department of Internal Medicine, UMDNJ-RWJ Medical School, Robert Wood Johnson Pl. 1, New Brunswick, 08903-0019, New Jersey, USA

    Ihor Gussak

  2. , Gordon K. Moe Scholar, Masonic Medical Research Laboratory, Bleecker Street, Utica, 13501-1787, New York, USA

    Charles Antzelevitch

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer-Verlag London

About this chapter

Cite this chapter

Vatta, M. (2013). Caveolae and Arrhythmogenesis. In: Gussak, I., Antzelevitch, C. (eds) Electrical Diseases of the Heart. Springer, London. https://doi.org/10.1007/978-1-4471-4881-4_18

Download citation

  • DOI: https://doi.org/10.1007/978-1-4471-4881-4_18

  • Published:

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-4471-4880-7

  • Online ISBN: 978-1-4471-4881-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation