Comprehensive Physiology Wiley Online Library

Cell Physiology and Cell Biology of Myocardial Cell Caveolae

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Caveolae
2 Ultrastructure
3 Morphometric Studies
4 Accessibility of the Lumens of Caveolae to Extracellular Macromolecules
5 Opening and Closure of Cardiac Myocyte Caveolae
6 Reversible Changes in Myocardial Cell Caveolar Volume and Surface Density in Hypertonic Solutions
7 Hypertonic Solutions Increase Mean Caveolar Neck Surface Density and Diameter
8 Water‐Channel Proteins in Mammalian Cardiac Myocytes
9 Temperature Dependence of the Co‐Localization of Aquaporin‐1 With Caveolin3
10 Physiological Role of Aquaporin‐1 in Human Cardiac Myocyte Caveolae
11 Relationship of Atrial Myocyte Caveolae to Atrial Granules
12 Localization of the Type B Atrial Natriuretic Peptide Receptor in Atrial Myocyte Caveolae
13 Co‐Localization of Endothelium‐Derived Nitric Oxide Synthase With Caveolin3 in Rat Cardiac Myocyte Caveolae
14 Endothelin and Protein Kinase C Isoforms in Cardiac Myocyte Caveolae
15 Immunoelectron Microscopic Localization of the Monocarboxylate Transporter, MCT‐1 in in Situ Rat Left Ventricular Myocytes
16 Neuregulin Binding to its Receptor in Cardiac Myocyte Caveolae
17 Adenosine A1 Receptor in Adult Cardiac Ventricular Myocytes
18 Exploration of Possible Interactions of Cardiac Myocyte Caveolae With Extracellular Matrix and Cytoskeleton‐Associated Proteins: Dystrophin and Dystroglycan
19 Dynamic Clustering of Sphingolipids and Cholesterol to form Functional “Rafts” in Cellular Membranes
20 Development of More Efficient, Specific, and Sensitive Methods for Identifying the Intracaveolar and Caveolae‐Bound Proteins of Cardiac Myocytes
21 Selected General Topics in Caveolar or Caveolae‐Relevant Biology
21.1 Physical considerations—caveolae as plasma membrane microdomains or plasma membrane‐associated microdomains
21.2 Caveolar Proteins
21.3 Other Caveolar Proteins: Reality vs. Artifact
Figure 1. Figure 1.

Electron micrograph of a longitudinally oriented lead‐ and uranium‐stained thin section through the cell surface of an unstretched, noncontracting isolated rat atrium incubated in physiological (isotonic) modified Krebs Henseleit (KH) solution at 37°C. Note multiple caveolar profiles beneath the sarcolemma, either open to the interstitial space (arrow) or apparently closed off from it.

Figs. , and are from Kordylewski et al.
Figure 2. Figure 2.

Specimen similar to shown in Fig. , illustrates caveolar profiles open to the interstitial space or apparently closed off from it by a narrow diaphragm.

Figure 3. Figure 3.

Electron micrograph of rat atrium prepared as for Fig. , but thin‐sectioned just below and parallel to the plasma membrane. Note multiple caveolar profiles (four or more) surrounding one caveolar neck in a “windmill” configuration, best seen just below the upper right corner of the micrograph.

Figure 4. Figure 4.

Electron micrograph of rat atrium prepared and thin‐sectioned as for Fig. just below and parallel to the plasma membrane, showing multiple caveolar profiles in series forming a continuous elongated structure with a common lumen.

Figure 5. Figure 5.

Electron micrograph of stretched atrial preparation incubated at 18°C with horeseradish peroxidase (HRP), stained histochemically for HRP, and counterstained with lead citrate. From the top downward note endocardial endothelial cell (E) with HRP‐containing vesicular profiles, subendocardial space (star) heavily stained with HRP, interstitial space between atrial myocytes (arrow) that is opacified with HRP, and atrial myocyte caveolae (arrowheads) filled with HRP.

Figure 6. Figure 6.

Unstretched isolated half rat atria either incubated for 5 min at 37°C in control solution made hypertonic by adding 150 mM sucrose (A) or in otherwise identical sucrose‐free isotonic control solution. Note swollen caveolae (A) and absence of swelling in isotonic control solution (B). Swelling in hypertonic sucrose was rapidly reversible by return to isotonic control solution (data not shown).

Figure 7. Figure 7.

Rat ventricular myocytes perfused in situ for 5 min. at 37°C through the coronary circulation on the Langendorff cannula with isotonic Krebs Henseleit solution (A), with an otherwise identical solution made hypertonic by adding 75 mM NaCl to isotonic control solution(B), or by reperfusing ventricles perfused with hypertonic solution with isotonic control solution (C). Note caveolar swelling in (B) and its regression in (C).

Figure 8. Figure 8.

Electron micrographs of replicas obtained by freeze‐fracture of rat hemi‐atria derived from the same atrium and incubated (before fixation, freeze‐fracture, and platinum shadowing) for five min., either in isotonic physiological saline (A) or in an otherwise identical solution made hypertonic by raising the total osmolarity by addition of 150 mmoles/L of sucrose (B). Quantitative analysis of multiple such samples yields statistical confirmation that exposure to hypertonic solutions raises the mean surface density of caveolar necks and also increases their mean diameter.

Figure 9. Figure 9.

Electron micrograph of a glutaraldehyde‐fixed, osmium tetroxide post–fixed ultra‐thin section of rat atrium stained with uranyl acetate and counter‐stained with lead citrate. The section shows the profile of a plasma membrane‐associated caveola apparently contiguous with an underlying atrial granule (star).

Figure 10. Figure 10.

Immunnoelectron micrograph showing a glutaraldehyde‐fixed, osmium tetroxide post‐fixed ultra‐thin section of rat atrium that has been stained with uranyl acetate and lead citrate and immunostained with antibody against rat alpha atrial natriuretic peptide. A stereo‐pair of this section (not shown) demonstrates colloidal gold decorating the inner edge of the caveolar membrane.

From Page et al. , with permission


Figure 1.

Electron micrograph of a longitudinally oriented lead‐ and uranium‐stained thin section through the cell surface of an unstretched, noncontracting isolated rat atrium incubated in physiological (isotonic) modified Krebs Henseleit (KH) solution at 37°C. Note multiple caveolar profiles beneath the sarcolemma, either open to the interstitial space (arrow) or apparently closed off from it.

Figs. , and are from Kordylewski et al.


Figure 2.

Specimen similar to shown in Fig. , illustrates caveolar profiles open to the interstitial space or apparently closed off from it by a narrow diaphragm.



Figure 3.

Electron micrograph of rat atrium prepared as for Fig. , but thin‐sectioned just below and parallel to the plasma membrane. Note multiple caveolar profiles (four or more) surrounding one caveolar neck in a “windmill” configuration, best seen just below the upper right corner of the micrograph.



Figure 4.

Electron micrograph of rat atrium prepared and thin‐sectioned as for Fig. just below and parallel to the plasma membrane, showing multiple caveolar profiles in series forming a continuous elongated structure with a common lumen.



Figure 5.

Electron micrograph of stretched atrial preparation incubated at 18°C with horeseradish peroxidase (HRP), stained histochemically for HRP, and counterstained with lead citrate. From the top downward note endocardial endothelial cell (E) with HRP‐containing vesicular profiles, subendocardial space (star) heavily stained with HRP, interstitial space between atrial myocytes (arrow) that is opacified with HRP, and atrial myocyte caveolae (arrowheads) filled with HRP.



Figure 6.

Unstretched isolated half rat atria either incubated for 5 min at 37°C in control solution made hypertonic by adding 150 mM sucrose (A) or in otherwise identical sucrose‐free isotonic control solution. Note swollen caveolae (A) and absence of swelling in isotonic control solution (B). Swelling in hypertonic sucrose was rapidly reversible by return to isotonic control solution (data not shown).



Figure 7.

Rat ventricular myocytes perfused in situ for 5 min. at 37°C through the coronary circulation on the Langendorff cannula with isotonic Krebs Henseleit solution (A), with an otherwise identical solution made hypertonic by adding 75 mM NaCl to isotonic control solution(B), or by reperfusing ventricles perfused with hypertonic solution with isotonic control solution (C). Note caveolar swelling in (B) and its regression in (C).



Figure 8.

Electron micrographs of replicas obtained by freeze‐fracture of rat hemi‐atria derived from the same atrium and incubated (before fixation, freeze‐fracture, and platinum shadowing) for five min., either in isotonic physiological saline (A) or in an otherwise identical solution made hypertonic by raising the total osmolarity by addition of 150 mmoles/L of sucrose (B). Quantitative analysis of multiple such samples yields statistical confirmation that exposure to hypertonic solutions raises the mean surface density of caveolar necks and also increases their mean diameter.



Figure 9.

Electron micrograph of a glutaraldehyde‐fixed, osmium tetroxide post–fixed ultra‐thin section of rat atrium stained with uranyl acetate and counter‐stained with lead citrate. The section shows the profile of a plasma membrane‐associated caveola apparently contiguous with an underlying atrial granule (star).



Figure 10.

Immunnoelectron micrograph showing a glutaraldehyde‐fixed, osmium tetroxide post‐fixed ultra‐thin section of rat atrium that has been stained with uranyl acetate and lead citrate and immunostained with antibody against rat alpha atrial natriuretic peptide. A stereo‐pair of this section (not shown) demonstrates colloidal gold decorating the inner edge of the caveolar membrane.

From Page et al. , with permission
References
 1. Anderson, R. G. W. Dissecting clathrin‐coated pits. Trends Cell Biol. 2: 177–199, 1992.
 2. Anderson, R. G. W. Caveolae: where incoming and outgoing messengers meet. Proc. Natl. Acad. Sci. U.S.A. 90: 10909–10913, 1993.
 3. Anderson, R. G. W., B. A. Kamen, R. G. Rothberg, and S. W. Lacey. Potocytosis: sequestration and transport of small molecules by caveolae. Science 255: 410–411, 1992.
 4. Balligand, J.‐L., R. A. Kelly, P. A. Marsden T. W. Smith, and T. Michel. Control of cardiac muscle cell function by an endogenous nitric oxide signalling system. Proc Natl Acad. Sci. U.S.A. 90: 347–351, 1993.
 5. Beaulieu, P., R. Cardinal, P. Page, F. Francoeur, J. Tremblay, and C. Lambert. Positive chronotropic and ionotropic effects of C‐type natriuretic peptide in dogs. Am. J. Physiol. 273: H1933–H1940, 1997.
 6. Birkenkamp‐Demtroeder, K., S. Bongartz, and J. D. Schipke. Expression of water channels in human heart. Faseb J. 89: 1998.
 7. Blobel, G. Intracellular protein topogenesis. Proc. Natl. Acad. Sci. U.S.A. 77: 1496–1500, 1980.
 8. Block, S. M. Leading the procession: new insights into kinesin motors. J. Cell Biol. 140: 1281–1284, 1998.
 9. Bloom, G. S. and L. S. B. Goldstein. Cruising along microtubule highways: how membranes move through the secretory pathway. J. Cell Biol. 140: 1277–1280, 1998.
 10. Brown, D. The tyrosine connection: how GPI‐anchored proteins activate T‐cells. Curr. Opin. Immunol. 5: 349–354, 1993.
 11. Carafoli, E. and D. Guerini. Molecular and cellular biology of plasma membrane calcium ATPase. Trends Cardiovasc. Med. 3: 177–184, 1993.
 12. Chaney, L. K. and B. S. Jacobson. Coating cells with colloidal silica for high yield isolation of plasma membrane sheets and identification of plasma membrane proteins. J. Biol Chem. 258: 10062–10072, 1983.
 13. Chang, M. P., W. G. Mallet, K. E. Mostov, and F. M. Brodsky. Adaptor self‐aggregation, adaptor receptor recognition and binding of alpha‐adaptin subunits to the plasma membrane contribute to recruitment of adaptor (AP2) components of clathrin‐coated pits. EMBO J. 12: 2169–2180, 1993.
 14. Chun, M., U. K. Liyanage, M. P. Lisanti, and H. F. Lodish. Signal transduction of a G protein‐coupled receptor in caveolae: colocalization of endothelin and its receptor with caveolin. Proc. Natl. Acad. Sci. U.S.A. 91: 11728–11732, 1994.
 15. Clemo, H. F., J. J. Feher, and C. N. Baumgarten. Modulation of rabbit ventricular cell volume and Na/K/2C1 cotransport by cGMP and atrial natriuretic factor. J. Gen. Physiol. 100: 89–114, 1992.
 16. Clemo, H. F., J. J. Feher, and C. M. Baumgarten. Modulation of rabbit ventricular cell volume and Na/K/2C1 cotransport by cGMP and atrial natriuretic factor. J. Gen. Physiol. 100: 89–114, 1992.
 17. Conrad, P. A., E. J. Smart, Y.‐S. Ying, R. G. W. Anderson, and G. S. Bloom. Caveolin cycles between plasma membrane caveolae and the Golgi complex by microtubule‐dependent and microtubule‐independent steps. J. Cell Biol. 131: 1421–1433, 1995.
 18. Cook, R. F. and M. Sargiacomo. Characterization of caveolinrich membrane domains isolated from an endothelial‐rich source: implications for human disease. J. Cell Biol. 126: 111–126, 1994.
 19. Cross, G. A. M. Glycolipid anchoring of plasma membrane proteins. Annu. Rev. Cell Biol. 6: 1–39, 1990.
 20. De Camilli, P., S. D. Emr, P. S. McPherson, and P. Novick. Phosphoinositides as regulators in membrane traffic. Science 271: 1533–1539, 1996.
 21. De Luca, A., M. Sargiacomo, A. Puca, G. Sgaramella, P. De Paolis, G. Frati, C. Morisco, B. Trimarco, M. Volpe, and G. Condorelli. Characterization of caveolae from rat heart: localization of postreceptor signal transduction molecules and their rearrangement after norepinephrine stimulation. J. Cell Biochem. 77: 529–539, 2000.
 22. Doyle, D. D., G. E. Goings, J. Upshaw‐Earley, E. Page, B. Ranscht, and H. C. Palfrey. T‐cadherin is a major glycophosphoinositol‐anchored protein associated with noncaveolar detergent‐insoluble domains of the cardiac sarcolemma. J. Biol. Chem. 273: 6937–6943, 1998.
 23. Doyle, D. D., S. K. Ambler, J. Upshaw‐Earley, A. Bastawropus, G. E. Goings and E. Page. Type B atrial natriuretic peptide receptor in cardiac myocyte caveolae. Circ. Res. 81: 86–91, 1997.
 24. Doyle, D. D., G. Goings, J. Upshaw‐Earley, S. K. Ambler, A. Mondul, H. C. Palfrey, and E. Page. Dystrophin associates with caveolae of rat cardiac myocytes. Circ. Res. 87: 480–488, 2000.
 25. Dupree, P., R. G. Parton, G. Raposo, T. V. Kurzchalia, and K. Simons. Caveolae and sorting in the trans‐Golgi network of epithelial cells. EMBO J. 12: 1597–1604, 1993.
 26. Edidin, M., S. C. Kuo, and M. P. Sheets. Lateral movements of membrane glycoproteins restricted by dynamic cytoplasmic barriers. Science 254: 1379–1382, 1991.
 27. Edidin, M., M. C. Zuniga, and M. P. Sheets. Truncation mutants define and locate cytoplasmic barriers to lateral mobility of membrane glycoproteins. Proc. Natl. Acad Sci. U.S.A. 91: 3378–3382, 1994.
 28. Engel, A., T. Walz, and P. Agre. The aquaporin family of membrane water channels. Curr. Opin. Struct. Biol. 4, 545–553, 1994.
 29. Englund, P. T. The structure and biosynthesis of glycosyl phosphatidylinositol protein anchors. Annu. Rev. Biochem. 62: 121–138, 1993.
 30. Fawcett, D. W. The ultrastructure of the cat myocardium. I. Ventricular papillary muscle. J. Cell Biol. 42: 1–45, 1969.
 31. Feron, O., L. Belhassen, L. Kobzig, T. W. Smith, R. A. Kelly, and T. Michel. Endothelial nitric oxide synthase targeting to caveolae: specific interactions with caveolin isoforms in cardiac myocytes and endothelial cells. J. Biol. Chem. 271: 22810–22814, 1996.
 32. Feron, O., T. W. Smith, T. Michel, and R. A. Kelly. Dynamic targeting of the agonist‐stimulated m2 muscarinic acetylcholine receptor to caveolae in cardiac myocytes. J. Biol. Chem. 272: 17744–17748, 1997.
 33. Feron, O., C. Dessy, D. J. Opel, M. A. Arstall, R. A. Kelly and T. Michel. Modulation of the endothelial nitric‐oxide synthase‐caveolin interaction in cardiac myocytes. Implications for the autonomic regulation of heart rate. J. Biol. Chem. 273: 30249–30254, 1998.
 34. Fouchier, F., P. Bastiani, T. Baltz, D. Aunis, and G. Rougon. Glycosylphosphatidylinositol is involved in the membrane attachment of proteins in granules of chromaffin cells. Biochem J. 256: 103–108, 1988.
 35. Fra, A. M., E. Williamson, K. Simons, and R. G. Parton. De novo formation of caveolae in lymphocytes by expression of VIP21‐caveolin. Proc. Natl. Acad. Sci. U.S.A. 92: 8655–8659, 1995.
 36. Friedrichson, T. and T. Kurzchalia. Microdomains of GPI‐anchored proteins in living cells revealed by crosslinking. Nature 394: 802–805, 1998.
 37. Frigeri, A., M. A. Gropper, F. Umenishi, M. Kawashima, D. Brown, and A. S. Verkman. Localization of MIWC and GLIP water channel homologs in neuromuscular, epithelial and glandular tissues. J. Cell. Sci. 108: 2993–3002, 1995.
 38. Fujimoto, T. Calcium pump of the plasma membrane is localized in caveolae. J. Cell Biol. 120: 1147–1149, 1993.
 39. Fujimoto, T., S. Nakada, A. Miyawaki, A. Mikoshiba, and K. Ogawa. Localization of inositol 1,4,5‐triphosphate receptor‐like protein in plasmalemmal caveolae. J. Cell Biol. 119: 1507–1513, 1992.
 40. Gabella, G. Inpocketings of cell membrane (caveolae) in the rat myocardium. J. Ultrastruct. Res. 65: 135–147, 1978.
 41. Galbiati, F., D. Volonte, D. Meani, G. Milligan, D. M. Lublin, M. P. Lisanti, and M. Parenti. The dually acylated NH2‐terminal domain of Gila is sufficient to target a green fluorescent protein reporter to caveolin‐enriched plasma membrane domains. Palmitoylation of caveolin‐1 is required for the recognition of dually acylated G‐protein a subunits in vivo. J. Biol. Chem. 274: 5843–5850, 1999.
 42. Glenney, J. R. and L. Zokas. Novel tyrosine kinase substrates from Rous sarcoma virus–transformed cells are present in the membrane cytoskeleton. J. Cell Biol. 108: 2401–2408, 1989.
 43. Glenney, J. R. The sequence of human caveolin reveals identity with VIP21, a component of transport vesiscles. FEBS Lett. 314: 45–48, 1992.
 44. Hansen, S. H., K. Sandvig, and B. van Deurs. Molecules internalized by clathrin‐independent endocytosis are delivered to endosomes containing transferrin receptors. J. Cell Biol. 123: 89–97, 1993.
 45. Harder, T., P. Scheiffele, P. Verkade, and K. Simons. Lipid domain structure of the plasma membrane revealed by patching of membrane components. J. Cell Biol. 141: 929–942, 1998.
 46. Hasegawa, H., T. Ma, W. Skach, and M. A. Matthay. Molecular cloning of a mercurial‐insensitive water channel expressed in selected water‐transporting tissues. J. Biol. Chem. 269: 5497–5500, 1994.
 47. Heuser, J. Three‐dimensional visualization of coated vesicle formation in fibroblasts. J. Cell Biol. 84: 560–563, 1980.
 48. Heuser, J. E., T. S. Reese, M. J. Dennis, Y. Jan, L. Jan, and L. Evans. Synaptic vesicle exocytosis captured by quick freezing and correlated with quantal transmitter release. J. Cell Biol. 81: 275–300, 1979.
 49. Hirose, M., Y. Furukawa, F. Kurogouchi, K. Nakajima, Y. Miyashita, and S. Chiba. C‐type natriuretic peptide increases myocardial contractility and sinus rate mediated by guanylyl cyclase‐linked natriuretic peptide receptors in isolated, blood‐perfused dog heart preparations. J. Pharm. Exp. Ther. 286: 70–76, 1998.
 50. Iida, H., W. M. Barron, and E. Page. Monensin turns on microtubule‐associated translocation of secretory granules in cultured atrial myocytes. Circ. Res. 62: 1159–1170, 1988.
 51. Ikezu, T., H. Ueda, B. D. Trapp, K. Nishiyama, J. F. Sha, D. Volonte, F. Galbiati, A. L. Byrd, G. Bassell, H. Serizawa, W. S. Lane, M. P. Lisanti, and T. Okamoto. Affinity‐purification and characterization of caveolins from the brain: differential expression of caveolin‐1,‐2, and‐3 in brain endothelial and astroglial cell types. Brain Res. 804: 177–192, 1998.
 52. Iwabuchi, K., K. Handa, and S. Hakomori. Separation of “glycolipid signaling domain” from caveolin‐containing membrane fraction in mouse melanoma B16 cells and its role in cell adhesion coupled with signaling. J. Biol. Chem. 273: 33766–33773, 1998.
 53. Izumi, T., Y. Shibata, and T. Yamamoto. The cytoplasmic surface structures of uncoated vesicles in various tissues of rat as revealed by quick‐freeze, deep‐etching replicas. J. Electron Microsc. 38: 47–53, 1989.
 54. Jacobson, K., E. D. Sheets, and R. Simson. Revisiting the fluid mosaic model of membranes. Science 268: 1441–1442, 1995.
 55. Johannsson, E., E. Nagelhus, K. J. A. McCullagh, O. M. Sejersted, T. W. Blackstad, A. Bonen, and O. P. Ottersen. Cellular and subcellular expression of the monocarboxylate transporter MCT1 in rat heart: a high‐resolution immunogold analysis. Circ. Res. 80: 400–407, 1997.
 56. Juen, P. S. T. and D. L. Garbers. 1992. Guanylyl cyclase‐linked receptors. Annu. Rev. Neurosci. 15: 193–225, 1992.
 57. Kelly, R., J.‐L. Balligand, and T. W. Smith. Nitric oxide and cardiac function. Circ. Res. 79: 363–380, 1996.
 58. Kordylewski, L., G. E. Goings, and E. Page. Rat atrial myocyte plasmalemmal caveolae in situ. Reversible experimental increases in caveolar size and in surface density of caveolar necks. Circ. Res. 73: 135–146, 1993.
 59. Korty, P. E., C. Brando, and E. M. Shevach. J. Immunol. 146: 4092–4098, 1991: [Korty et al.] CD59 functions as a signal‐transducing molecule for human T‐cell activation.
 60. Kreis, T. E. Regulation of vesicular and tubular membrane traffic of the Golgi complex by coat proteins. Curr. Opin. Cell Biol. 4: 609–615, 1992.
 61. Kurzchalia, T. V., P. Dupree, R. G. Parton, R. Kellner, H. Virta, M. Lehnert, and K. Simons. VIP21, a 21‐KD membrane protein is an integral component of trans‐Golgi network‐derived transport vesicles. J. Cell Biol. 118: 1003–1114, 1992.
 62. Kurzchalia, T. V., E. Hartmann, and P. Dupree. Guilt by insolubility—does a protein's detergent insolubility reflect a caveolar location?. Trends Cell Biol. 5: 187–189, 1995.
 63. Kurzchalia, T. V. and R. G. Parton. Membrane microdomains and caveolae. Curr. Opin. Cell Biol. 11: 424–431, 1999.
 64. Kusumi, A., Y. Sako, and M. Yamamoto. Confined membrane diffusion of membrane receptors as studied by single particle tracking (nanovid microscopy). Effects of calcium‐induced differentiation in cultured epithelial cells. Biophys. J. 65: 2021–2040, 1993.
 65. Lang, D. M., S. Lommel, M. Jung, R. Ankerhold, B. Petraush, U. Laessing, M. F. Wiechers, H. Plattner, and C. A. Stuermer. Identification of reggie‐t and reggie‐2 as plasmamembrane‐associated proteins which cocluster with activated GPI‐linked cell adhesion molecules in non‐caveolar micropatces in neurons. J. Neurobiol. 37: 502–523, 1998.
 66. Lasley, R. D., P. Narayan, A. Uittenbogaard, and E. J. Smart. Activated cardiac adenosine A1 receptors translocate out of caveolae. J. Biol. Chem. 275: 4417–4421, 2000.
 67. LeBel, D. and M. Beattie. The major protein of pancreatic zymogen granule membranes (GP‐2) is anchored via covalent bonds to phosphatidylinositol. Biochem. Biophys. Res. Commun. 154: 818–823, 1988.
 68. Lee, S. J., S. Z. Kim, X. Cui, S. H. Kim, K. S. Lee, Y. J. Chung, and K. W. Cho. C‐type natriuretic peptide inhibits ANP secretion and atria dynamics in perfused atria: NPR‐B‐cGMP signalling. Am. J. Physiol. Heart Cir. Physiol. 278: H208–H221, 2000.
 69. Levin, K. R. and E. Page. Quantitative studies on plasmalemmal folds and caveolae of rabbit ventricular myocardial cells. Circ. Res. 46: 244–255, 1980.
 70. Li, S., T. Okamoto, M. Chun, M. Sargiacomo, J. E. Casanova, S. H. Hansen, I. Nishimoto, and M. P. Lisanti. Evidence for a regulated interaction between heterotrimeric G proteins and caveolin. J. Biol. Chem. 270: 15693–15701, 1995.
 71. Li, S., K. S. Song, and M. P. Lisanti. Expression and characterization of recombinant caveolin. Purification by polyhistidine tagging and cholesterol‐dependent incorporation into defined lipid membranes. J. Biol. Chem. 271: 568–573, 1996.
 72. Lisanti, M. P. and E. Rodriguez‐Boulan. Glycophospholipid membrane anchoring provides clues to the mechanism of protein sorting in polarized epithelial cells. Trends Biochem. Sci. 15: 113–118, 1990.
 73. Lisanti, M. P., P. E. Scherer, J. Vidugiriene, Z. L. Tang, A. Hermanowski‐Vosatka, Y.‐H. Tu, R. F. Cook, and M. Sargiacomo. Characterization of caveolin‐rich membrane domains isolated from an endothlial‐rich source: implications for human disease. J. Cell Biol. 126: 111–1126, 1994.
 74. Lisanti, M. P., Z. L. Tang, and M. Sargiacomo. Caveolin forms a hetero‐oligomeric protein complex that interacts with an apical GPI‐linked protein: implications for the biogenesis of caveolae. J. Cell Biol. 123: 595–604, 1993.
 75. Loo, J. A., and R. R. Ogorzalek Loo. Electrospray ionization mass spectroscopy of peptides and proteins. In Electrospray Ionization Mass Spectrometry, edited by R. B. Cole. New York: John Wiley & Sons, Inc., 1997: 385–419.
 76. Low, M. G. The glycosyl‐phosphatidylinositol anchor of membrane proteins. Biochim. Biophys. Acta 988: 427–454, 1989.
 77. Ma, T., B. Yang, and A. S. Verkman. Cloning of a novel and urea‐permeable aquaporin from mouse expressed strongly in colon, placenta, liver, and heart. Biochem. Biophys. Res. Commun. 240: 324–328, 1997.
 78. Marsh, M. and D. Cutler. Membrane traffic: taking the Rabs off endocytosis. Curr. Biol. 3: 30–33, 1993.
 79. Mayor, S. and F. R. Maxfield. Insolubility and redistribution of GPI‐anchored proteins at the cell surface after detergent treatment. Mol. Biol. Cell 6: 929–944, 1995.
 80. Mayor, S., K. G. Rothberg, and F. R. Maxfield. Sequestration of GPI‐anchored proteins in caveolae triggered by cross‐linking. Science 264: 1948–1951, 1994.
 81. McConville, M. J. and M. A. Ferguson. The structure, biosynthesis and function of glycosylated phosphatidylinositols in the parasitic protozoa and higher eukaryotes. Biochem. J. 294: 305–324, 1993.
 82. McNally, E. M., E. de Sa Moreira, D. J. Duggan, C. G. Bonnemann, M. P. Lisanti, H. G. W. Lidov, M. Vainzof, M. R. Passos‐Bueno, E. P. Hoffman, M. Zatz, and L. M. Kinkel. Caveolin‐3 in muscular dystrophy. Hum. Mol. Genet. 7: 871–877, 1998.
 83. Melancon, P. Vesicle traffic: “G Whizz.” Curr. Biol. 3: 230–233, 1993.
 84. Melkonian, K. A., A. G. Ostermeyer, J. Z. Chen, M. G. Roth, and D. A. Brown. Role of lipid modifications in targeting proteins to detergent‐resistant membrane rafts. Many raft proteins are acylated, while few are prenylated. J. Biol. Chem. 274: 3910–3917, 1999.
 85. Minetti, C., F. Sotgia, C. Bruno, P. Scartezzini, P. Broda, M. Bado, E. Masetti, M. Mazzocco, A. Egeo, M. A. Donati, D. Volonte, F. Galbiati, G. Cordone, F. D. Bricarelli, M. P. Lisanti, and F. Zara. Mutations in the caveolin‐3 gene cause autosomal dominant limb‐girdle muscular dystrophy. Nature Genet. 18: 365–368, 1998.
 86. Monier, S., R. G. Parton, F. Vogel, J. Behlke, A. Henske, and T. V. Kurzchalia. VIP21‐caveolin, a membrane protein constituent of the caveolar coat, oligomerizes in vivo and in vitro. Mol. Biol. Cell 6: 911–927, 1995.
 87. Morgan, A. and R. D. Burgoyne. A role for soluble NSF attachment proteins (SNAPS) in regulated exocytosis in adrenal chromaffin cells. Embo. J. 14: 232–239, 1995.
 88. Murata, M., J. Peranen, R. Schreiner, F. Wieland, T. Kurzchalia, and K. Simons. VIP21/caveolin is a cholesterol‐binding protein. Proc. Natl. Acad. Sci. U.S.A. 92: 10339–10343, 1995.
 89. Oh, P. and J. E. Schnitzer. Immunoisolation of caveolae with high affinity antibody binding to the oligomeric caveolin cage. J. Biol. Chem. 274: 23144–23154, 1999.
 90. Narayan, P., H. H. Valdivia, R. M. Mentzer Jr., and R. D. Lasley. Adenosine A1 receptor stimulation antagonizes the negative inotropic effects of PKC activator dioctanoylglycerol. J. Mol. Cell Cardiol. 30: 913–921, 1998.
 91. Ohyama, Y., K. Miyamoto, Y. Morishita, Y. Matsuda, Y. Saito, N. Minamino, K. Kangawa, and H. Matsuo. Stable expression of natriuretic peptide receptors: effects of HS‐142–1, a non‐peptide ANP antagonist. Biochem. Biophys. Res. Comm. 189: 336–342, 1992.
 92. Okamoto, T., A. Schlegel, P. E. Scherer, and M. P. Lisanti. Caveolins, a family of scaffolding proteins for organizing “preassembled signaling complexes” at the plasma membrane. J. Biol. Chem. 273: 5419–5422, 1998.
 93. Ostrom, R. S. and P. A. Insel. Signal transduction pathways in caveolae. Sci. Med. Jan/Feb: 44–53, 2000.
 94. Page, E. Tubular systems in Purkinje cells of the cat heart. J. Ultrastruct. Res. 17: 72–83, 1966.
 95. Page, E., G. E. Goings, J. Upshaw‐Earley, and D. A. Hanck. Endocytosis and uptake of lucifer yellow by cultured atrial myocytes and isolated intact atria from adult rats. Regulation and subcellular localization. Circ. Res. 75: 335–346, 1994.
 96. Page, E., G. E. Goings, B. Power, and J. Upshaw‐Earley. Ultrastructural features of atrial peptide secretion. Am. J. Physiol. 251 (Heart Circ. Physiol. 20): H340–H348, 1986.
 97. Page, E., G. E. Goings, B. Power, and J. Upshaw‐Earley. Basal and stretch‐augmented natriuretic peptide secretion by quiescent rat atria. Am. J. Physiol. 259 (Cell Physiol. 28): C801–C818, 1990.
 98. Page, E., J. Upshaw‐Earley, and G. E. Goings. Localization of atrial natriuretic peptide in caveolae of in situ atrial myocytes. Circ. Res. 75: 949–954, 1994.
 99. Page, E., J. Upshaw‐Earley, and G. E. Goings. Permeability of rat atrial endocardium, epicardium, and myocardium to large molecules: stretch‐dependent effects. Circ. Res. 71: 159–173, 1992.
 100. Page, E., J. Upshaw‐Earley, G. E. Goings, and D. A. Hanck. Effect of external Ca2+ concentration on stretch‐augmented natriuretic peptide secretion by rat atria. Am. J. Physiol. 260 (Cell Physiol. 29): C756–C762, 1991.
 101. Page, E., J. Winterfield, G. E. Goings, A. Bastawrous, J. Upshaw‐Earley, and D. D. Doyle. Water channel proteins in rat cardiac myocyte caveolae: osmolarity‐dependent reversible internalization. Am. J. Physiol. 274 (Heart Circ. Physiol. 43): H1988–H2000, 1998.
 102. Palade, G. E. Fine structure of blood capillaries. J. Appl. Physics 24, 1414, 1953 (Abstr).
 103. Parton, R. G. Ultrastructural localization of gangliosides; GM‐1 is concentrated in caveolae. J. Histochem. Cytochem. 42: 155–166, 1994.
 104. Parton, G. and K. Simons. Digging into caveolae. Science 269: 1398–1399, 1995.
 105. Peters, K.‐R., W. W. Carley, and G. E. Palade. Endothelial plasmalemmal vesicles have a characteristic striped bipolar surface structure. J. Cell Biol. 101: 2233–2238, 1985.
 106. Picot, D., P. J. Loll, and R. M. Garavito. The X‐ray crystal structure of the membrane protein prostaglandin H‐2 synthase‐1. Nature 367: 243–249, 1994.
 107. Poulos, A. C., J. E. Rash, and J. K. Elmund. Ultrarapid freezing reveals that skeletal muscle caveolae are semipermanent structures. J. Ultrastruct. Res. 96: 114–124, 1986.
 108. Ranscht, B., and M. T. Dours‐Zimmermann. T‐cadherin, a novel cadherin cell adhesion molecule in the nervous system, lacks the conserved cytoplasmic region. Neuron 7: 391–402, 1991.
 109. Rayns, D. G., F. O. Simpson and W. S. Bertaud. Surface features of striated muscle. I. Guinea‐pig cardiac muscle. J. Cell Sci. 3: 467–474, 1968.
 110. Robinson, P. J. Phosphatidylinositol membrane anchors and T‐cell activation. Immunol. Today 12: 35–41, 1991.
 111. Rostgaard, J. and O. Behnke. Fine structural localization of adenine nucleoside. Phosphatase activity in the sarcoplasmic reticulum and the T system of rat myocardium. J. Ultrastruct. Res. 12: 579–591, 1965.
 112. Rothberg, K. G., J. E. Heuser, W. C. Donzell, Y.‐S. Ying, J. R. Glenney, and R. G. W. Anderson. Caveolin, a protein component of caveolae membrane coats. Cell 68: 673–682, 1992.
 113. Rothberg, K. G., Y. Ying, J. F. Kolhouse, B. A. Kamen, and R. G. W. Anderson. The glycophospholipid‐linked folate receptor internalizes folate without entering the clathrincoated pit endocytic pathway. J. Cell Biol. 110: 637–649, 1990.
 114. Rothberg, K. G., Y.‐S. Ying, B. A. Kamen, and R. G. W. Anderson. Cholesterol controls the clustering of the glycophospholipid‐anchored membrane receptor for 5‐methyltetrahydrofolate. J. Cell Biol. 111: 2931–2938, 1990.
 115. Rothman, J. E. and F. T. Wieland. Protein by transport vesicles. Science 272: 227–234, 1996.
 116. Rybin, V. O., X. Xu, and S. F. Steinberg. Activated protein kinase C isoforms target to cardiomyocyte caveolae. Stimulation of local protein phosphorylation. Circ. Res. 84: 980–988, 1999.
 117. Rybin, V. O., X. Xu, M. P. Lisanti, and S. F. Steinberg. Differential tergeting of β‐adrenergic receptor subtypes and adenylyl cyclase to cardiomyocyte caveolae. J. Biol. Chem. 275: 41447–41457, 2000.
 118. Sako, Y. and A. Kusumi. Compartmentalized structure of the plasma membrane for receptor movements as revealed by a nanometer‐level motion analysis. J. Cell Biol. 125: 1251–1264, 1994.
 119. Sandvig, K., S. Olsnes, O. W. Petersen, and B. van Deurs. Acidification of the cytosol inhibits endocytosis from coated pits. J. Cell Biol. 105: 679–689, 1987.
 120. Sargiacomo, M., P. E. Scherer, Z.‐L. Tang, E. Kubler, K. S. Song, M. C. Sanders, and M. C. Lisanti. Proc. Natl. Acad. Sci. U.S.A. 92: 9407–9411, 1995. Oligomeric structure of caveolin: implications for caveolae membrane organization.
 121. Sargiacomo, M., M. Sudol, Z. L. Tang, and M. P. Lisanti. Signal transducing molecules and glycosyl‐phosphatidylinositol‐linked prteins form a caveolin‐rich insoluble complex in MDCK cells. J. Cell Biol. 122: 789–807, 1993.
 122. Schekman, R. and L. Orci. Coat proteins and vesicle budding. Science 271: 1526–11533, 1996.
 123. Scherer, P. E., Z. L. Tang, M. Chun, M. Sargiacomo, H. F. Lodish, and M. P. Lisanti. Caveolin isoforms differ in their N‐terminal protein sequence and subcellular distribution. J. Biol. Chem. 270: 16395–16401, 1995.
 124. Schipke, J. D., K. Birkenkamp‐Demtroeder, and U. Schwanke. Myocardial hibernation: another view. Z. Kardiol. 89: 259–263, 2000.
 125. Schnitzer, J. E. Update on the cellular and molecular basis of capillary permeability. Trends Cardiovasc. Med. 3: 124–130, 1993.
 126. Schnitzer, J. E., J. Allard, and P. Oh. NEM inhibits transcytosis, endocytosis, and capillary permeability: implication of caveolae fusion in endothelia. Am. J. Physiol. 268 (Heart Circ. Physiol. 37): H48–H55, 1995.
 127. Schnitzer, J. E., J. Liu, and P. Oh. Endothelial caveolae have the molecular transport machinery for vesicle budding, docking, and fusion including VAMP, NSF, SNAP, annexins, and GTPases. J. Biol. Chem. 270: 14399–14404, 1995.
 128. Schnitzer, J. E., D. P. McIntosh, A. M. Dvorak, J. Liu, and P. Oh. Separation of caveolae from associated microdomains of GPI‐anchored proteins. Science 269: 1435–1439, 1995.
 129. Schnitzer, J. E., P. Oh, E. Pinney, and J. Allard. Filipin‐sensitive caveolae‐mediated transport in endothelium: reduced transcytosis, scavenger endocytosis, and capillary permeability of select macromolecules. J. Cell Biol. 127: 1217–1132, 1994.
 130. Severs, N. J. Localization of cholesterol in the Golgi apparatus of cardiac muscle cells. Experientia 37: 1195–1197, 1981.
 131. Severs, N. J. Comparison of the response of myocardial muscle and capillary endothelial nuclear membranes to the cholesterol probe filipin. J. Submicrosc. Cytol. 14: 441–452, 1982.
 132. Severs, N. J. Caveolae: static inpocketings of the plasma membrane, dynamic vesicles or plain artifact?. J. Cell Sci. 90: 341–348, 1988.
 133. Shaul, P. W. and R. G. W. Anderson. Role of plasmalemmal caveolae in signal transduction. Am. J. Physiol. 275 (Lung Cell Mol. Physiol. 19): L843–L851, 1998.
 134. Simionescu, N. and M. Simionescu. Receptor‐mediated transcytosis of albumin: identification of albumin binding proteins in the plasma membrane of capillary endothelium. Microcirculation, vol. 1, edited by M. Tsuchiya et al. New York: Elsevier, 1987: 67–82.
 135. Simons, K. and E. Ikonen. Functional rafts in cell membranes. Nature 387: 569–572, 1997.
 136. Simons, K. and A. Wandinger‐Ness. Polarized sorting in epithelia. Cell 62: 207–210, 1990.
 137. Simson, R., B. Yang, P. Doherty, S. Moore, F. Walsh, and K. Jacobson. The mosaic structure of cell membranes revealed by transient confinement of GPI‐linked NCAM‐125. Biophys. J. 68: 436, 1995 (abstr).
 138. Singer, S. J. and G. L. Nicolson. The fluid mosaic model of the structure of cell membranes. Science 175: 720–731, 1972.
 139. Smart, E. J., Y.‐S. Ying, P. A. Conrad, and R. G. W. Anderson. Caveolin moves from caveolae to the Golgi apparatus in response to cholesterol oxidation. J. Cell Biol. 127: 1185–1197, 1994.
 140. Smart, E. J., Y.‐S. Ying, C. Mineo, and R. G. W. Anderson. A detergent‐free method for purifying caveolae membrane from tissue culture cells. Proc. Natl. Acad. Sci. U.S.A. 92: 10104–10108, 1995.
 141. Smart, E. J., G. A. Graf, M. A. McNiven, W. C. Sessa, J. A. Engelman, P. E. Scherer, T. Okamoto, and M. P. Lisanti. Caveolins, liquid‐ordered domains, and signal transduction. Mol. Cell. Biol. 19: 7289–7304, 1999.
 142. Sommer, J. R., P. C. Dolber, and I. Taylor. Filipin‐sterol complexes in the membranes of cardiac muscle. J. Ultrastruct. Res. 80: 98–103, 1982.
 143. Sommer, J. R. and E. A. Johnson. Comparative ultrastructure of cardiac membrane specializations. A review. Am. J. Cardiol. 25: 184–194, 1970.
 144. Sommer, J. R., E. A. Johnson, N. R. Wallace, and R. Nassar. Cardiac muscle following quick‐freezing: preservation of in vivo ultrastructure and geometry with special emphasis on intercellular clefts in the intact frog heart. J. Mol. Cell. Cardiol. 20: 285–302, 1988.
 145. Song, K. S., S. Li, T. Okamoto, L. A. Quillam, M. Sargiacomo, and M. P. Lisanti. Copurification and direct interaction of Ras with caveolin, an integral membrane protein of caveolae microdomains: detergent‐free purification of caveolae microdomains. J. Biol. Chem. 271: 9690–9697, 1996.
 146. Song, K. S., P. E. Scherer, Z. L. Tang, T. Okamoto, S. Li, M. Chafel, C. Chu, D. S. Kohtz, and M. P. Lisanti. Expression of caveolin‐3 in skeletal, cardiac, and smooth muscle cells. Caveolin‐3 is a component of the sarcolemma and cofractionates with dystrophin and dystrophin‐associated glycoproteins. J. Biol. Chem. 271: 15160–15165, 1996.
 147. Sperelakis, N., Tohse, N., Ohya, Y., and Masuda, H. Cyclic GMP regulation of calcium slow channels in cardiac muscle and vascular smooth muscle cells. Adv. Pharmacol. 26: 217–151, 1994.
 148. Stan, R.‐V., W. G. Roberts, D. Predescu, K. Ihida, S. Saican, L. Ghitescu and G. E. Palade. Immunoisolation and partial characterization of endothelial plasmalemmal vesiscles (caveolae). Mol. Biol. Cell 8: 595–605, 1997.
 149. Tang, Z., P. E. Scherer, T. Okamoto, K. Song, C. Chu, D. S. Kohtz, I. Nishimoto, H. F. Lodish, and M. P. Lisanti. Molecular cloning of caveolin‐3, a novel member of the caveolin gene family expressed predominantly in muscle. J. Biol. Chem. 271: 2255–2261, 1996.
 150. Thompson, L. F., J. M. Ruedi, A. Glass, M. G. Low, and A. H. Lucas. Antibodies to 5′‐nucleotidase (CD73), a glycophosphatidylinositol‐anchored protein, cause human peripheral blood T‐cells to proliferate. J. Immunol 143: 1815–1821, 1989.
 151. Thompson, T. E. and T. W. Tillack. Organization of glycosphingolipids in bilayers and plasma membranes of mammalian cells. Annu. Rev. Biophys. Chem. 14: 361–386, 1985.
 152. Tohse, N., H. Nakaya, Y. Takeda, and M. Kanno. Cyclic GMP‐mediated inhibition of L‐type Ca2+ channel activity by human natriuretic peptide in rabbit heart cells. Br. J. Pharmacol. 114: 1076–1082, 1994.
 153. Tran, D., J.‐L. Carpentier, F. Sawamo, P. Goren, and L. Orci. Ligands internalized through coated or non‐coated invaginations follow a common intracellular pathway. Proc. Natl. Acad. Sci. U.S.A. 84: 7957–7961, 1987.
 154. Van Deurs, B., O. W. Petersen, S. Olsnes, and K. Sandvig. The ways of endocytosis. Int. Rev. Cytol. 117: 131–177, 1989.
 155. Van Os, C. H., P. M. T. Deen, and J. A. Dempster. Aquaporins: water selective channels in biological membranes. Molecular structure and tissue distribution. Biochim. Biophys. Acta 1197: 291–309, 1994.
 156. Vinten, J., J. Tranum‐Jensen, and M. Foldstedlund. The caveolin‐3 isoform of muscle is abundant in astrocytes. Mol. Biol. Cell. 8 [Suppl.] 208a, 1997.
 157. Verkman, A. S., A. N. van Hoek, Ma, T. A. Frigeri, W. R. Skach, A. Mitra, B. K. Tamarappoo, and J. Farinas. Water transport across mammalian cell membranes. Am. J. Physiol. 270 (Cell Physiol. 39): C12–C30, 1996.
 158. Watts, C. and M. Marsh. Endocytosis: what goes on and how?. J. Cell Sci. 103: 1–08, 1992.
 159. Way, M., and R. G. Parton. M‐caveolin, a muscle‐specific caveolin‐related protein. FEBS Lett. 376: 108–112, 1995.
 160. Waugh, M. G., D. Lawson, S. K. Tan, and J. J. Hsuan. Phosphatidylinositol 4‐phosphate synthesis in immunoisolated caveolae‐like vesicles and low density non‐caveolar membranes. J. Biol. Chem. 273: 17115–17121, 1998.
 161. Waugh, M. G., D. Lawson, and J. J. Hsuan. Epidermal growth factor receptor activation is localized within low‐buoyant density, non‐caveolar membrane domains. Biochem J. 337: 591–597, 1999.
 162. Yamada, E. The fine structure of the gall bladder epithelium of the mouse. J. Biophys. Biochem. Cytol. 1: 445–458, 1955.
 163. Zeidel, M. L., S. Nielsen, B. L. Smith, S. V. Ambudkar, A. B. Maunsbach, and P. Agre. Ultrastructure, pharmacological inhibition, and transport selectivity of aquaporin channel‐forming integral protein in proteoliposomes. Biochem. J. 33: 1606–1615, 1994.
 164. Zhao, Y., D. R. Sawyer, R. R. Baglia, D. J. Opel, X. Han, M. A. Marchionni, and R. A. Kelly. Neuregulins promote survival and growth of cardiac myocytes. Persistence of erbB2 and erbB4 expression in neonatal and adult ventricular myocytes. J. Biol. Chem. 273: 10261–10269, 1998.
 165. Zhao, Y., O. Feron, C. Dessy, X. Han, M. A. Marchionni, R. A. Kelly. Neuregulin signaling in the heart: dynamic targeting of erbB4 to caveolar microdomains in cardiac myocytes. Circ. Res. 84: 1380–1387, 1999.

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite

Ernest Page, Hiroshi Iida, Donald D. Doyle. Cell Physiology and Cell Biology of Myocardial Cell Caveolae. Compr Physiol 2011, Supplement 6: Handbook of Physiology, The Cardiovascular System, The Heart: 145-168. First published in print 2002. doi: 10.1002/cphy.cp020103