Functional properties of mouse connexin30.2 expressed in the conduction system of the heart

被引:104
作者
Kreuzberg, MM
Söhl, GS
Kim, JS
Verselis, VK
Willecke, K
Bukauskas, FF
机构
[1] Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10461 USA
[2] Univ Ulsan, Asan Med Ctr, Dept Pathol, Seoul, South Korea
[3] Univ Bonn, Inst Genet, Abt Mol Genet, D-5300 Bonn, Germany
关键词
connexin; gap junctions; mCx30.2; sinoatrial node; atrioventricular node;
D O I
10.1161/01.RES.0000169271.33675.05
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Gap junction channels composed of connexin (Cx) 40, Cx43, and Cx45 proteins are known to be necessary for impulse propagation through the heart. Here, we report mouse connexin30.2 ( mCx30.2) to be a new cardiac connexin that is expressed mainly in the conduction system of the heart. Antibodies raised to the cytoplasmic loop or the C-terminal regions of mCx30.2 recognized this protein in mouse heart as well as in HeLa cells transfected with wild-type mCx30.2 or mCx30.2 fused with enhanced green fluorescent protein (mCx30.2-EGFP). Immunofluorescence analyses of adult hearts yielded positive signals within the sinoatrial node, atrioventricular node, and A-V bundle of the cardiac conduction system. Dye transfer studies demonstrated that mCx30.2 and mCx30.2-EGFP channels discriminate poorly on the basis of charge, but do not allow permeation of tracers > 400 Da. Both mCx30.2 and mCx30.2-EGFP gap junctional channels exhibited weak sensitivity to transjunctional voltage (V-j) and a single channel conductance of approximate to 9 pS, which is the lowest among all members of the connexin family measured in HeLa cell transfectants. HeLa mCx30.2-EGFP transfectants when paired with cells expressing Cx40, Cx43, or Cx45 formed functional heterotypic gap junction channels that exhibited low unitary conductances ( 15 to 18 pS), rectifying open channel I-V relations and asymmetric Vj dependence. The electrical properties of homo- and hetero-typic junctions involving mCx30.2 may contribute to slow propagation velocity in nodal tissues and directional asymmetry of excitation spread in the AV nodal region.
引用
收藏
页码:1169 / 1177
页数:9
相关论文
共 26 条
[1]   Replacement of connexin40 by connexin45 in the mouse -: Impact on cardiac electrical conduction [J].
Alcoléa, S ;
Jarry-Guichard, T ;
de Bakker, J ;
Gonzàlez, D ;
Lamers, W ;
Coppen, S ;
Barrio, L ;
Jongsma, H ;
Gros, D ;
van Rijen, H .
CIRCULATION RESEARCH, 2004, 94 (01) :100-109
[2]   Gap junction channel gating [J].
Bukauskas, FF ;
Verselis, VK .
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 2004, 1662 (1-2) :42-60
[3]   BIOPHYSICAL PROPERTIES OF GAP JUNCTION CHANNELS FORMED BY MOUSE CONNEXIN40 IN INDUCED PAIRS OF TRANSFECTED HUMAN HELA-CELLS [J].
BUKAUSKAS, FF ;
ELFGANG, C ;
WILLECKE, K ;
WEINGART, R .
BIOPHYSICAL JOURNAL, 1995, 68 (06) :2289-2298
[4]   Coupling asymmetry of heterotypic connexin 45/connexin 43-EGFP gap junctions: Properties of fast and slow gating mechanisms [J].
Bukauskas, FF ;
Angele, AB ;
Verselis, VK ;
Bennett, MVL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (10) :7113-7118
[5]   Gating properties of gap junction channels assembled from connexin43 and connexin43 fused with green fluorescent protein [J].
Bukauskas, FF ;
Bukauskiene, A ;
Bennet, MVL ;
Verselis, VK .
BIOPHYSICAL JOURNAL, 2001, 81 (01) :137-152
[6]  
Coppen SR, 1998, CIRC RES, V82, P232
[7]   Connexins in mammalian heart function [J].
Gros, DB ;
Jongsma, HJ .
BIOESSAYS, 1996, 18 (09) :719-730
[8]  
Kirchhoff S, 2000, CIRC RES, V87, P399
[9]  
Krüger O, 2000, DEVELOPMENT, V127, P4179
[10]  
Lo CW, 2000, CIRC RES, V87, P346