Title |
Cardiac BIN1 folds T-tubule membrane, controlling ion flux and limiting arrhythmia
|
---|---|
Published in |
Nature Medicine, May 2014
|
DOI | 10.1038/nm.3543 |
Pubmed ID | |
Authors |
TingTing Hong, Huanghe Yang, Shan-Shan Zhang, Hee Cheol Cho, Mariya Kalashnikova, Baiming Sun, Hao Zhang, Anamika Bhargava, Michael Grabe, Jeffrey Olgin, Julia Gorelik, Eduardo Marbán, Lily Y Jan, Robin M Shaw |
Abstract |
Cardiomyocyte T tubules are important for regulating ion flux. Bridging integrator 1 (BIN1) is a T-tubule protein associated with calcium channel trafficking that is downregulated in failing hearts. Here we find that cardiac T tubules normally contain dense protective inner membrane folds that are formed by a cardiac isoform of BIN1. In mice with cardiac Bin1 deletion, T-tubule folding is decreased, which does not change overall cardiomyocyte morphology but leads to free diffusion of local extracellular calcium and potassium ions, prolonging action-potential duration and increasing susceptibility to ventricular arrhythmias. We also found that T-tubule inner folds are rescued by expression of the BIN1 isoform BIN1+13+17, which promotes N-WASP-dependent actin polymerization to stabilize the T-tubule membrane at cardiac Z discs. BIN1+13+17 recruits actin to fold the T-tubule membrane, creating a 'fuzzy space' that protectively restricts ion flux. When the amount of the BIN1+13+17 isoform is decreased, as occurs in acquired cardiomyopathy, T-tubule morphology is altered, and arrhythmia can result. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Switzerland | 1 | 33% |
United Kingdom | 1 | 33% |
Unknown | 1 | 33% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 2 | 67% |
Scientists | 1 | 33% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | <1% |
France | 1 | <1% |
Switzerland | 1 | <1% |
Unknown | 178 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 39 | 22% |
Researcher | 29 | 16% |
Student > Master | 18 | 10% |
Student > Bachelor | 17 | 9% |
Student > Doctoral Student | 14 | 8% |
Other | 37 | 20% |
Unknown | 27 | 15% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 53 | 29% |
Agricultural and Biological Sciences | 34 | 19% |
Medicine and Dentistry | 29 | 16% |
Engineering | 9 | 5% |
Chemistry | 6 | 3% |
Other | 23 | 13% |
Unknown | 27 | 15% |