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The loss of CAR (green) expression leads to cardiac arrhythmia because connexins (red) are no longer held in place at heart AV nodes.
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A cell contact protein found in the heart does more than provide structural support, according to Lisewski et al. (page 2369). It also helps maintain a steady heartbeat.
In developing or injured heart muscle, a cell–cell adhesion protein known as the Coxsackievirus–adenovirus receptor (CAR) helps growing muscle fibers stick to each other and settle into place. The relatively low levels of CAR in adult hearts suggest that they've outgrown the need for it. But the authors now find that this bit of CAR keeps ion channels called connexins in place, thus aiding the transmission of electrical connections between heart cells.
Decreasing CAR expression in the heart, the group found, did not disrupt the structural stability of the organ but triggered an erratic heartbeat. Electrical signals within each heart chamber were normal, but they were delayed in passing from atria to ventricles.
Electrical signals pass between the chambers through a cell cluster called the atrial-ventricular (AV) node, via ion channels made of connexins 45. The AV node cells of CAR-deficient mice had fewer of these connexins, which drifted throughout the cell membrane instead of clustering at gap junctions, where they belong. Although it's possible that CAR-driven signals induce connexin gene expression, the recent discovery that the two proteins bind to each other suggests instead that CAR might pin down connexins in adjacent gap junctions, thereby preventing their mislocalization and subsequent degradation.
The findings might explain the association between cardiac arrhythmia and CAR loss seen in patients who develop autoantibodies against CAR or who become infected with Coxsackievirus. The group is now trying to confirm that this arrhythmia is due to a connexin disturbance at the AV node. HB
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