Heart researchers used to speculate that the BIN1 protein was responsible for making the T-tubules themselves, but Shaw's group found that the pockets exist even in the absence of the protein.
"In this study, using specialized microscopes, we could see that even though the T-tubules were still there, they looked very different. We discovered that although BIN1 does not create the tubule, it shapes it. The tubule was thought to be a very smooth dip of the membrane, but we now know there is a very complex folding, where BIN1 sculpts microfolds within the tubule," Shaw said.
"The tiny folds are very important because they can trap the chemicals that control heart rhythm," he added. "A little bit of trapping of calcium and potassium ions slightly changes the concentration of the environment just outside the cell, and these subtle changes are very protective for the heart. They actually alter the electrophysiology, protecting against arrhythmias like those that occur in heart failure. About 300,000 people die each year of heart failure, and rhythm abnormalities are the dominant cause of death."
The findings present a new perspective on heart failure development and rhythm abnormalities.
"We cardiologists historically have said, 'The heart gets big and loses its shape, and this somehow affects the electrical circuitry.' But this study suggests that even before the heart becomes enlarged, there is a decrease in BIN1. We knew loss of BIN1 predicted arrhythmia. Now we know why: Without BIN1, the protective microfolds go away," Shaw said. "We believe that when a patient's heart is stressed for any reason heart attack, infection, disease the 'program' wit
|Contact: Sally Stewart|
Cedars-Sinai Medical Center