Cardiac T-Tubule Microanatomy and Function.

Publisher: American Physiological Society Country of Publication: United States NLM ID: 0231714 Publication Model: Print Cited Medium: Internet ISSN: 1522-1210 (Electronic) Linking ISSN: 00319333 NLM ISO Abbreviation: Physiol Rev Subsets: MEDLINE

Publication: Bethesda, MD : American Physiological Society
Original Publication: Washington [etc.] American Physiological Society.

Myocytes, Cardiac/*metabolism ; Myocytes, Cardiac/*ultrastructure ; Sarcolemma/*metabolism ; Sarcolemma/*ultrastructure; Animals ; Humans

Unique to striated muscle cells, transverse tubules (t-tubules) are membrane organelles that consist of sarcolemma penetrating into the myocyte interior, forming a highly branched and interconnected network. Mature t-tubule networks are found in mammalian ventricular cardiomyocytes, with the transverse components of t-tubules occurring near sarcomeric z-discs. Cardiac t-tubules contain membrane microdomains enriched with ion channels and signaling molecules. The microdomains serve as key signaling hubs in regulation of cardiomyocyte function. Dyad microdomains formed at the junctional contact between t-tubule membrane and neighboring sarcoplasmic reticulum are critical in calcium signaling and excitation-contraction coupling necessary for beat-to-beat heart contraction. In this review, we provide an overview of the current knowledge in gross morphology and structure, membrane and protein composition, and function of the cardiac t-tubule network. We also review in detail current knowledge on the formation of functional membrane subdomains within t-tubules, with a particular focus on the cardiac dyad microdomain. Lastly, we discuss the dynamic nature of t-tubules including membrane turnover, trafficking of transmembrane proteins, and the life cycles of membrane subdomains such as the cardiac BIN1-microdomain, as well as t-tubule remodeling and alteration in diseased hearts. Understanding cardiac t-tubule biology in normal and failing hearts is providing novel diagnostic and therapeutic opportunities to better treat patients with failing hearts.
(Copyright © 2017 the American Physiological Society.)

Cell. 2009 Apr 17;137(2):191-6. (PMID: 19379681)
J Anat. 1978 Sep;127(Pt 1):125-40. (PMID: 701190)
N Engl J Med. 2009 Dec 03;361(23):2241-51. (PMID: 19920051)
Trends Mol Med. 2014 Jun;20(6):353-62. (PMID: 24636942)
J Biomed Biotechnol. 2010;2010:503906. (PMID: 20396394)
Ann N Y Acad Sci. 1998 Sep 16;853:20-30. (PMID: 10603933)
Cell. 2000 May 12;101(4):365-76. (PMID: 10830164)
J Mol Cell Cardiol. 1971 Aug;2(3):211-220. (PMID: 5117216)
J Biol Chem. 2003 Jun 27;278(26):23480-6. (PMID: 12707260)
Biochem Biophys Res Commun. 1994 Jan 28;198(2):701-6. (PMID: 8297381)
J Physiol. 2003 Mar 1;547(Pt 2):441-51. (PMID: 12562899)
Nat Cell Biol. 2010 Sep;12(9):902-8. (PMID: 20729836)
JACC Basic Transl Sci. 2016 Jan-Feb;1(1-2):14-28. (PMID: 27104217)
Eur Biophys J. 2012 Jun;41(6):491-503. (PMID: 22466899)
Circ Res. 2012 Mar 2;110(5):669-74. (PMID: 22302787)
J Biol Chem. 2000 Dec 15;275(50):39193-9. (PMID: 10973973)
Circ Res. 2012 Feb 17;110(4):588-97. (PMID: 22253411)
J Mol Cell Cardiol. 2014 Feb;67:38-48. (PMID: 24345421)
Circ Res. 2005 Mar 18;96(5):543-50. (PMID: 15705962)
Mol Pharmacol. 1995 Feb;47(2):322-9. (PMID: 7870040)
Am J Physiol. 1993 Jun;264(6 Pt 1):C1587-93. (PMID: 8333507)
Circ Heart Fail. 2012 May 1;5(3):357-65. (PMID: 22456061)
Cardiovasc Res. 2015 Sep 1;107(4):466-77. (PMID: 26109584)
Circ Res. 2003 Jun 13;92(11):1182-92. (PMID: 12805236)
Circ Res. 1999 Jan 8-22;84(1):43-52. (PMID: 9915773)
Cell Calcium. 1997 Dec;22(6):431-8. (PMID: 9502192)
Cell Tissue Res. 1991 May;264(2):293-8. (PMID: 1715241)
Adv Cancer Res. 1991;57:1-46. (PMID: 1950701)
Cell Calcium. 1998 May;23(5):269-79. (PMID: 9681190)
J Physiol. 2001 Dec 15;537(Pt 3):979-92. (PMID: 11744770)
Am J Physiol Heart Circ Physiol. 2002 Sep;283(3):H1123-33. (PMID: 12181143)
J Cell Physiol. 2011 Sep;226(9):2235-43. (PMID: 21660947)
Biochem Biophys Res Commun. 1985 Apr 16;128(1):449-56. (PMID: 3985981)
Am J Physiol. 1998 Aug;275(2 Pt 1):C459-67. (PMID: 9688600)
J Biol Chem. 2001 Jun 15;276(24):21425-33. (PMID: 11259414)
Cardiovasc Res. 2013 May 1;98(2):216-24. (PMID: 23345264)
Cell Calcium. 2005 Mar;37(3):233-43. (PMID: 15670870)
Biochemistry. 2006 Oct 31;45(43):12917-28. (PMID: 17059209)
J Mol Cell Cardiol. 2012 Sep;53(3):409-19. (PMID: 22728217)
Exp Anim. 2013;62(3):211-7. (PMID: 23903056)
Nat Commun. 2014 Dec 09;5:5647. (PMID: 25487648)
J Am Coll Cardiol. 2004 Dec 7;44(11):2192-201. (PMID: 15582318)
Cardiovasc Res. 2008 Apr 1;78(1):71-8. (PMID: 18203708)
Heart Rhythm. 2012 May;9(5):812-20. (PMID: 22138472)
Biochem Biophys Res Commun. 2005 Sep 9;334(4):1135-40. (PMID: 16038878)
Circ Res. 2009 Oct 23;105(9):876-85. (PMID: 19762679)
Cardiovasc Res. 2007 Jan 1;73(1):92-100. (PMID: 17157829)
Cardiovasc Res. 2013 May 1;98(2):162-4. (PMID: 23504549)
Cardiovasc Res. 2001 Feb 1;49(2):298-307. (PMID: 11164840)
J Cell Biol. 2009 Mar 23;184(6):923-33. (PMID: 19307602)
Eur J Transl Myol. 2014 Dec 24;25(1):4747. (PMID: 26913143)
J Biol Chem. 1997 Dec 12;272(50):31453-8. (PMID: 9395479)
Traffic. 2000 Apr;1(4):326-41. (PMID: 11208118)
Proc Natl Acad Sci U S A. 2014 Nov 18;111(46):16598-603. (PMID: 25368181)
Prog Biophys Mol Biol. 2008 Jan-Apr;96(1-3):258-80. (PMID: 17888503)
Rinsho Shinkeigaku. 2004 Jun;44(6):375-8. (PMID: 15293763)
Am J Transplant. 2010 Apr;10(4 Pt 2):1035-46. (PMID: 20420651)
Cell Mol Life Sci. 2013 Dec;70(24):4695-710. (PMID: 23846763)
J Cell Sci. 2014 May 1;127(Pt 9):2106-19. (PMID: 24569881)
J Cell Biol. 2016 Jun 20;213(6):705-18. (PMID: 27298325)
J Clin Invest. 2007 Jul;117(7):1805-13. (PMID: 17607357)
Mol Cell Biol. 2003 Jun;23(12):4295-306. (PMID: 12773571)
Am J Physiol. 1983 Jul;245(1):C1-14. (PMID: 6346892)
J Neurosci. 2011 Sep 21;31(38):13682-94. (PMID: 21940459)
J Cell Biol. 1963 Feb;16:297-313. (PMID: 13938025)
Circ Res. 2009 Sep 11;105(6):527-36. (PMID: 19679837)
Proc Natl Acad Sci U S A. 1999 Aug 17;96(17):9689-94. (PMID: 10449755)
J Cell Biochem. 2015 Nov;116(11):2541-51. (PMID: 25939245)
J Cell Biol. 1975 Mar;64(3):734-40. (PMID: 1080153)
Science. 1990 Apr 20;248(4953):283. (PMID: 2326638)
Circulation. 2016 Jan 26;133(4):388-97. (PMID: 26733606)
Elife. 2015 Feb 25;4:null. (PMID: 25714924)
Physiology (Bethesda). 2007 Jun;22:167-73. (PMID: 17557937)
Science. 2010 Mar 26;327(5973):1653-7. (PMID: 20185685)
Biophys J. 1994 Nov;67(5):1942-56. (PMID: 7858131)
Circ Res. 1999 Sep 3;85(5):415-27. (PMID: 10473671)
J Biol Chem. 1996 Jun 21;271(25):15160-5. (PMID: 8663016)
J Ultrastruct Res. 1967 Jan;17(1):72-83. (PMID: 6017361)
Nature. 2002 Jan 10;415(6868):198-205. (PMID: 11805843)
Exp Clin Cardiol. 2003 Summer;8(2):67-70. (PMID: 19641652)
Eur Heart J. 2012 Jul;33(14):1787-847. (PMID: 22611136)
Nat Med. 2014 Jun;20(6):624-32. (PMID: 24836577)
Cell Rep. 2013 Nov 14;5(3):611-8. (PMID: 24210816)
FASEB J. 2012 Jan;26(1):63-72. (PMID: 21948246)
Circ Res. 2004 Apr 2;94(6):e61-70. (PMID: 15016728)
Biochim Biophys Acta. 2016 Jul;1863(7 Pt B):1839-47. (PMID: 26578114)
J Biol Chem. 2004 Mar 12;279(11):10206-14. (PMID: 14699099)
Exp Cell Res. 2009 Apr 1;315(6):1015-28. (PMID: 19101541)
Cardiovasc Res. 2008 Jan 15;77(2):237-44. (PMID: 18006490)
Proc Natl Acad Sci U S A. 1971 Jul;68(7):1465-6. (PMID: 5283936)
Circ Res. 1999 Feb 19;84(3):266-75. (PMID: 10024300)
Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):9137-42. (PMID: 15178757)
J Appl Physiol (1985). 2006 Oct;101(4):1170-6. (PMID: 16763106)
Circ Res. 2012 Aug 3;111(4):402-14. (PMID: 22723297)
J Biol Chem. 1987 Nov 15;262(32):15637-42. (PMID: 3680217)
Biophys J. 2008 Aug;95(4):2053-62. (PMID: 18487298)
JAMA. 2009 Jan 28;301(4):383-92. (PMID: 19176440)
Am J Physiol Heart Circ Physiol. 2011 Nov;301(5):H1996-2005. (PMID: 21841013)
Proc Natl Acad Sci U S A. 2007 Sep 18;104(38):14958-63. (PMID: 17848521)
Trends Cell Biol. 2004 Apr;14(4):206-13. (PMID: 15066638)
Science. 1997 May 2;276(5313):800-6. (PMID: 9115206)
J Physiol. 2006 Jul 15;574(Pt 2):519-33. (PMID: 16709642)
Circ Res. 2006 Mar 17;98(5):667-74. (PMID: 16484618)
Circulation. 2001 Aug 7;104(6):688-93. (PMID: 11489776)
J Biol Chem. 1997 Dec 5;272(49):30984-92. (PMID: 9388246)
Cell. 2007 Feb 9;128(3):547-60. (PMID: 17289573)
J Muscle Res Cell Motil. 2007;28(2-3):115-21. (PMID: 17572852)
J Clin Invest. 2012 Jan;122(1):280-90. (PMID: 22133878)
Proc Natl Acad Sci U S A. 2006 May 9;103(19):7500-5. (PMID: 16648270)
Nature. 1997 Nov 6;390(6655):88-91. (PMID: 9363896)
Cardiovasc Res. 2013 May 1;98(2):225-32. (PMID: 23345265)
Nature. 1955 Dec 3;176(4492):1068. (PMID: 13272749)
Am J Physiol. 1998 Sep;275(3 Pt 2):H852-60. (PMID: 9724289)
J Biol Chem. 2003 Jul 11;278(28):25558-67. (PMID: 12730233)
Cardiovasc Res. 2013 May 1;98(2):204-15. (PMID: 23393229)
Cell. 2002 Dec 27;111(7):943-55. (PMID: 12507422)
Circ Res. 1980 Feb;46(2):244-55. (PMID: 7351042)
J Biol Chem. 2011 Apr 8;286(14):12617-26. (PMID: 21216955)
J Pharmacol Sci. 2013;123(2):167-75. (PMID: 24096881)
Circulation. 2011 Feb 1;123(4):e18-e209. (PMID: 21160056)
J Biol Chem. 2001 Aug 31;276(35):33175-80. (PMID: 11432863)
Am J Pathol. 2014 Jan;184(1):248-59. (PMID: 24177035)
Pflugers Arch. 1996 Apr;431(6):814-27. (PMID: 8927497)
Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1800-5. (PMID: 9050859)
Arch Biochem Biophys. 1982 May;215(2):628-37. (PMID: 7092244)
Proc Natl Acad Sci U S A. 2012 Apr 10;109(15):5815-9. (PMID: 22451916)
J Mol Med (Berl). 2007 Nov;85(11):1203-14. (PMID: 17828519)
Curr Opin Cardiol. 2005 May;20(3):189-93. (PMID: 15861006)
J Biol Chem. 2002 Jun 21;277(25):22883-8. (PMID: 11959863)
Am J Anat. 1965 Jul;117:1-17. (PMID: 14345833)
Science. 2002 Aug 16;297(5584):1193-6. (PMID: 12183633)
J Muscle Res Cell Motil. 2006;27(5-7):297-306. (PMID: 16897575)
Pflugers Arch. 2002 Jul;444(4):532-8. (PMID: 12136273)
Circ Res. 1995 Aug;77(2):361-9. (PMID: 7614722)
J Biol Chem. 1995 Dec 15;270(50):30036-44. (PMID: 8530407)
Hum Mol Genet. 2014 Jul 1;23(13):3566-78. (PMID: 24549043)
Heart Rhythm. 2012 Jun;9(6):961-7. (PMID: 22300662)
Sci STKE. 2001 Oct 16;2001(104):re15. (PMID: 11604549)
J Cell Biol. 1969 Jul;42(1):1-45. (PMID: 4891913)
Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1607-12. (PMID: 11171998)
J Mol Med (Berl). 2014 May;92(5):453-63. (PMID: 24590001)
Nature. 2003 May 8;423(6936):168-72. (PMID: 12736685)
FEBS Lett. 1995 May 8;364(2):198-202. (PMID: 7750570)
J Cell Biol. 2001 May 14;153(4):699-708. (PMID: 11352932)
Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):19621-6. (PMID: 24218620)
Proc Natl Acad Sci U S A. 2009 Apr 21;106(16):6854-9. (PMID: 19342485)
Circ Res. 2002 Nov 29;91(11):1023-30. (PMID: 12456488)
Biophys J. 2013 Jun 4;104(11):L22-4. (PMID: 23746531)
Cardiovasc Res. 2004 Apr 1;62(1):63-73. (PMID: 15023553)
Circ Res. 1994 Apr;74(4):669-78. (PMID: 8137503)
Am J Physiol Heart Circ Physiol. 2002 Jul;283(1):H181-5. (PMID: 12063289)
J Biol Chem. 1999 Apr 2;274(14):9760-70. (PMID: 10092665)
J Mol Cell Cardiol. 1999 Dec;31(12):2207-13. (PMID: 10640448)
Circulation. 2000 Jun 6;101(22):2586-94. (PMID: 10840009)
Circ Heart Fail. 2009 Sep;2(5):482-9. (PMID: 19808379)
J Mol Cell Cardiol. 1997 Nov;29(11):3035-42. (PMID: 9405178)
Proc Natl Acad Sci U S A. 2012 Mar 6;109(10):3997-4001. (PMID: 22355118)
J Muscle Res Cell Motil. 2015 Apr;36(2):205-14. (PMID: 25694159)
Circ Res. 2012 Mar 30;110(7):978-89. (PMID: 22328533)
Circ Res. 2008 Feb 15;102(3):338-46. (PMID: 18079411)
J Clin Invest. 2010 Jan;120(1):266-79. (PMID: 20038810)
Biophys J. 2003 Nov;85(5):3388-96. (PMID: 14581240)
Annu Rev Physiol. 2015;77:505-24. (PMID: 25293528)
Mol Biol Cell. 2009 Jan;20(1):400-9. (PMID: 19005216)
FASEB J. 2010 Sep;24(9):3321-9. (PMID: 20430793)
J Mol Cell Cardiol. 2012 Jun;52(6):1240-8. (PMID: 22406428)
Science. 1993 Oct 29;262(5134):740-4. (PMID: 8235594)
Prog Biophys Mol Biol. 2008 Jan-Apr;96(1-3):244-57. (PMID: 17881039)
Nature. 2006 Apr 13;440(7086):935-9. (PMID: 16612384)
Biochem J. 1994 Apr 15;299 ( Pt 2):359-65. (PMID: 8172595)
Neuroscience. 2007 Jan 19;144(2):531-46. (PMID: 17101229)
Circ Res. 1979 Aug;45(2):260-7. (PMID: 376173)
Dev Biol. 2014 Mar 15;387(2):179-90. (PMID: 24440153)
Cardiovasc Res. 2008 Apr 1;78(1):45-52. (PMID: 18178574)
Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):4073-8. (PMID: 11891345)
Cell Calcium. 2005 Nov;38(5):515-26. (PMID: 16137761)
Biophys J. 2000 Nov;79(5):2682-91. (PMID: 11053140)
J Cell Sci. 2001 Mar;114(Pt 5):987-98. (PMID: 11181181)
Circ Res. 2010 Aug 20;107(4):520-31. (PMID: 20576937)
Annu Rev Genet. 1986;20:361-84. (PMID: 3028245)
Prog Biophys Mol Biol. 2008 Oct-Nov;98(2-3):149-60. (PMID: 19351512)
Biochim Biophys Acta. 1987 Sep 25;921(2):398-404. (PMID: 3115305)
Crit Rev Biochem Mol Biol. 2004 May-Jun;39(3):125-45. (PMID: 15596548)
J Biol Chem. 1983 Jan 10;258(1):464-71. (PMID: 6217205)
Circulation. 2004 Mar 23;109(11):1421-7. (PMID: 15007009)
PLoS Biol. 2005 Dec;3(12):e423. (PMID: 16292983)
Cancer Res. 1997 Aug 1;57(15):3258-63. (PMID: 9242458)
Nature. 2003 Feb 6;421(6923):634-9. (PMID: 12571597)
Physiol Rev. 2009 Apr;89(2):411-52. (PMID: 19342611)
Circulation. 2007 Feb 6;115(5):e69-171. (PMID: 17194875)
PLoS Biol. 2010 Feb 16;8(2):e1000312. (PMID: 20169111)
Am J Physiol Heart Circ Physiol. 2008 Aug;295(2):H667-76. (PMID: 18552167)
Circ Res. 2000 Dec 8;87(12):1172-9. (PMID: 11110775)
Cell. 2007 Nov 30;131(5):861-72. (PMID: 18035408)
Biophys J. 2004 Apr;86(4):2121-8. (PMID: 15041652)
J Physiol. 1996 Feb 15;491 ( Pt 1):81-97. (PMID: 9011624)
Cardiovasc Res. 2003 Jun 1;58(3):535-48. (PMID: 12798426)
J Cell Biol. 1997 Jun 16;137(6):1355-67. (PMID: 9182667)
Circ Res. 2014 Jul 7;115(2):252-62. (PMID: 24786399)
Circ Res. 2000 Nov 24;87(11):1040-7. (PMID: 11090550)
PLoS One. 2011;6(9):e24404. (PMID: 21912691)
Orphanet J Rare Dis. 2010 Dec 03;5:35. (PMID: 21129173)
PLoS One. 2015 Sep 14;10(9):e0136922. (PMID: 26368922)
J Cell Biol. 1970 Jan;44(1):1-19. (PMID: 4901374)
Z Zellforsch Mikrosk Anat. 1957;45(6):702-46. (PMID: 13456982)
Science. 2010 Dec 10;330(6010):1536-40. (PMID: 21148390)
J Cell Biol. 1962 Jan;12:91-100. (PMID: 13913207)
PLoS One. 2011 Mar 09;6(3):e17901. (PMID: 21408028)
J Am Coll Cardiol. 2012 Oct 2;60(14):1297-313. (PMID: 22975230)
Circulation. 2007 Jul 31;116(5):497-505. (PMID: 17638928)
Circ Res. 2002 Feb 8;90(2):165-73. (PMID: 11834709)
Circ Res. 2014 Dec 5;115(12):986-96. (PMID: 25332206)
Science. 1996 Mar 15;271(5255):1589-92. (PMID: 8599116)
J Mol Cell Cardiol. 2012 Feb;52(2):376-87. (PMID: 21888911)
Exp Physiol. 2009 May;94(5):509-19. (PMID: 19297389)
N Engl J Med. 2008 May 15;358(20):2148-59. (PMID: 18480207)
J Mol Cell Cardiol. 2013 May;58:5-12. (PMID: 23201225)
Neuron. 1998 May;20(5):1017-26. (PMID: 9620705)
Cardiovasc Res. 2008 Jan 15;77(2):315-24. (PMID: 18006436)
J Mol Biol. 2005 Aug 19;351(3):653-61. (PMID: 16023669)
J Biol Chem. 2004 Oct 22;279(43):44690-4. (PMID: 15304481)
Circulation. 2010 Feb 23;121(7):e46-e215. (PMID: 20019324)
Cardiovasc Res. 2006 Jul 1;71(1):22-9. (PMID: 16650839)
J Cell Sci. 2009 Apr 1;122(Pt 7):1005-13. (PMID: 19295127)
Am J Physiol. 1978 Nov;235(5):C147-58. (PMID: 364994)
Science. 2004 Jan 23;303(5657):495-9. (PMID: 14645856)
Biochemistry. 2012 Dec 4;51(48):9658-66. (PMID: 23145875)
N Engl J Med. 2006 Jul 20;355(3):251-9. (PMID: 16855265)
Trends Mol Med. 2003 Aug;9(8):327-30. (PMID: 12928033)
Curr Mol Pharmacol. 2015;8(2):206-22. (PMID: 25966694)
Eur J Heart Fail. 2012 Jun;14(6):571-80. (PMID: 22467752)
Philos Trans A Math Phys Eng Sci. 2006 May 15;364(1842):1187-206. (PMID: 16608703)
Proc R Soc Lond B Biol Sci. 1971 Jun 15;178(1050):1-27. (PMID: 4397265)
J Muscle Res Cell Motil. 2007;28(4-5):231-41. (PMID: 17940841)
EMBO J. 2011 Aug 31;30(17):3501-15. (PMID: 21878992)
J Biol Chem. 1981 Aug 10;256(15):8140-8. (PMID: 6455421)
J Mol Cell Cardiol. 2012 Jan;52(1):113-24. (PMID: 21930133)
Circ Res. 2010 Mar 5;106(4):748-56. (PMID: 20110531)
Circulation. 2011 Mar 8;123(9):979-88. (PMID: 21339484)
Am J Pathol. 2009 Dec;175(6):2299-308. (PMID: 19875504)

R01 HL133286 United States HL NHLBI NIH HHS; R01 HL094414 United States HL NHLBI NIH HHS; R21 HL109750 United States HL NHLBI NIH HHS

Date Created: 20161125 Date Completed: 20170310 Latest Revision: 20181113

20221213

PMC6151489

10.1152/physrev.00037.2015

27881552