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Preventing Fatal Arrhythmias

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Science's STKE  13 Apr 2004:
Vol. 2004, Issue 228, pp. tw135-TW135
DOI: 10.1126/stke.2282004TW135

The precise mechanisms that cause cardiac arrhythmias have been hard to pin down. Wehrens et al. describe the effects of the experimental drug JTV519, a derivative of 1,4-benzothiazepine, which causes increased binding of the protein calstabin2 to the ryanodine receptor. The ryanodine receptor is a calcium-release channel that contributes to muscle contraction. When calstabin binds, the channel is held in its closed state and calcium is not released. Mice that have decreased amounts of calstabin2 are prone to arrhythmias. Treatment with JTV519 protected such animals from fatal arrhythmias, but the drug had no effect on animals that completely lacked the calstabin2 protein. Thus, JTV519 appears to prevent arrhythmias by increasing association of calstabin with ryanodine-receptor channels, plugging the leak of calcium thought to initiate the life-threatening abnormal contractions.

X. H. T. Wehrens, S. E. Lehnart, S. R. Reiken, S.-X. Deng, J. A. Vest, D. Cervantes, J. Coromilas, D. W. Landry, A. R. Marks, Protection from cardiac arrhythmia through ryanodine receptor-stabilizing protein calstabin2. Science 304, 292-296 (2004). [Abstract] [Full Text]

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