Ordered assembly of the adhesive and electrochemical connections within newly formed intercalated disks in primary cultures of adult rat cardiomyocytes.
The intercalated disk (ID) is a complex structure that electromechanically couples adjoining cardiac myocytes into a functional syncitium. The integrity of the disk is essential for normal cardiac function, but how the diverse elements are assembled into a fully integrated structure is not well understood. In this study, we examined the assembly of new IDs in primary cultures of adult rat cardiac myocytes. From 2 to 5 days after dissociation, the cells flatten and spread, establishing new cell-cell contacts in a manner that recapitulates the in vivo processes that occur during heart development and myocardial remodeling. As cells make contact with their neighbors, transmembrane adhesion proteins localize along the line of apposition, concentrating at the sites of membrane attachment of the terminal sarcomeres. Cx43 gap junctions and ankyrin-G, an essential cytoskeletal component of voltage gated sodium channel complexes, were secondarily recruited to membrane domains involved in cell-cell contacts. The consistent order of the assembly process suggests that there are specific scaffolding requirements for integration of the mechanical and electrochemical elements of the disk. Defining the relationships that are the foundation of disk assembly has important implications for understanding the mechanical dysfunction and cardiac arrhythmias that accompany alterations of ID architecture.
Geisler
Sarah B
SB
Division of Pediatric Cardiology, Department of Pediatrics and Communicable Diseases, University of Michigan, 1150 West Medical Center Dr., Ann Arbor, MI 48109, USA.
Green
Kathleen J
KJ
Isom
Lori L
LL
Meshinchi
Sasha
S
Martens
Jeffrey R
JR
Delmar
Mario
M
Russell
Mark W
MW
D000818:Animals; D051186:Armadillo Domain Proteins / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D002478:Cells, Cultured; D018031:Connexin 43 / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D005260:Female; D006651:Histocytochemistry; D007365:Intercellular Junctions / Q000378:metabolism* / Q000648:ultrastructure; D008856:Microscopy, Fluorescence; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D015222:Sodium Channels / Q000378:metabolism
D051186:Armadillo Domain Proteins; D015820:Cadherins; D018031:Connexin 43; D015222:Sodium Channels
J Cell Biol. 1998 Jun 1;141(5):1229-41
9606214
Circ Res. 1997 Jan;80(1):88-94
8978327
J Mol Cell Cardiol. 2001 Feb;33(2):359-71
11162139
J Cell Biol. 1997 Nov 3;139(3):773-84
9348293
Circulation. 2004 Oct 5;110(14):1879-84
15451782
Trends Cardiovasc Med. 2003 Jan;13(1):30-8
12554098
J Biol Chem. 2004 Dec 10;279(50):52744-52
15466474
J Mol Cell Cardiol. 2009 Aug;47(2):203-9
19394342
Eur J Cell Biol. 2007 Mar;86(3):127-42
17275137
Cardiovasc Res. 1999 Dec;44(3):507-17
10690282
J Cell Biol. 2008 May 19;181(4):605-13
18474624
Neuron. 2000 Nov;28(2):365-8
11144347
Histochem Cell Biol. 2008 Apr;129(4):463-78
18219491
Cell. 1995 Mar 10;80(5):805-11
7889574
Circ Res. 2009 Sep 11;105(6):523-6
19661460
J Biol Chem. 2002 Jul 19;277(29):26681-8
11997395
Circ Res. 1999 Jul 23;85(2):154-67
10417397
Circulation. 2004 Oct 12;110(15):2163-7
15466643
Proc Natl Acad Sci U S A. 2004 Dec 14;101(50):17533-8
15579534
Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):6210-5
11972032
Differentiation. 2004 Oct;72(8):419-33
15606501
J Biol Chem. 1996 May 3;271(18):10904-9
8631907
J Cell Sci. 2000 Nov;113 Pt 21:3851-9
11034912
Neuroscientist. 2008 Dec;14(6):571-83
18940784
Cell. 2007 Feb 9;128(3):547-60
17289573
Circulation. 2005 Dec 20;112(25):3823-32
16344387
Circulation. 2001 Mar 6;103(9):1303-10
11238277
Eur J Cell Biol. 2006 Feb;85(2):69-82
16406610
J Cell Biol. 1992 Mar;116(5):1197-209
1740472
J Ultrastruct Res. 1982 Dec;81(3):358-74
6891003
Expert Opin Ther Targets. 2008 Sep;12(9):1191-203
18694383
J Cell Sci. 1996 May;109 ( Pt 5):1143-54
8743961
Circulation. 1998 Feb 24;97(7):651-60
9495300
Prog Cardiovasc Dis. 2008 Jul-Aug;51(1):31-43
18634916
Circulation. 2003 Dec 16;108(24):3000-5
14662701
J Cell Biol. 2001 May 14;153(4):763-72
11352937
J Cardiovasc Electrophysiol. 2008 Nov;19(11):1212-4
18554203
Tissue Cell. 1985;17(5):605-48
3904080
Am J Pathol. 1991 Oct;139(4):801-21
1656760
Methods Cell Biol. 1997;52:307-22
9379958
Nat Genet. 1999 Sep;23(1):20-1
10471492
Circ Res. 2001 May 11;88(9):933-9
11349003
J Cell Biol. 2008 Jan 14;180(1):173-86
18180363
Heart Rhythm. 2008 Dec;5(12):1715-23
19084810
J Cell Sci. 2006 Aug 15;119(Pt 16):3435-42
16882687
J Biol Chem. 1999 Jun 25;274(26):18145-8
10373410
J Invest Dermatol. 1995 Jan;104(1):27-32
7528244
Eur J Cell Biol. 2008 Jul;87(7):399-411
18261826
J Mol Cell Cardiol. 2008 Mar;44(3):597-606
18201716
J Invest Dermatol. 1994 Jun;102(6):870-7
8006450
Nat Genet. 2004 Nov;36(11):1162-4
15489853
Eur J Cell Biol. 2008 Jul;87(7):413-30
18420304
Circ Res. 2007 Sep 28;101(7):703-11
17673670
Circ Res. 2004 Nov 12;95(10):1035-41
15499029