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An irregular heartbeat makes exercise deadly

The results of a study in mice that was conducted by researchers from Vanderbilt University has provided a potential explanation for why the heartbeat of humans lacking the protein cardiac calsequestrin (CASQ2) is irregular, and potentially fatal, only during exercise and not at other times.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a life-threatening disease characterized by an irregular heartbeat during exercise. CPVT can be caused by mutations in the gene encoding CASQ2, which is a Ca2+-binding protein found in the Ca2+ storage facility of the muscle cells of the heart. Paradoxically, although CASQ2 is thought to have a crucial role in regulating contraction of the heart, individuals lacking both copies of CASQ2 and whose hearts contract relatively normally have been identified. In a study that appears online on August 24 in advance of publication in the September print issue of the Journal of Clinical Investigation, Bjrn Knollmann and colleagues generated Casq2-deficient mice to help explain this paradox. Similar to humans lacking CASQ2, Casq2-deficient mice showed normal heart contraction under basal conditions, but both exercise and exposure to catecholamines (which are chemicals such as epinephrine made by the body during exercise and stress) induced an irregular heartbeat. The authors found that the lack of Casq2 was compensated for in several ways, including a substantial increase in the volume of the Ca2+ storage facility in the muscle cells of the heart, such that under basal conditions the heartbeat was regular. However, when exposed to catecholamines, a lack of Casq2 caused Ca2+ to spontaneously leak from its storage facility and trigger an inappropriate heartbeat. This study identifies the mechanisms behind the irregular heartbeats caused by a lack of Casq2, and might explain why the hearts of humans lacking CASQ2 beat relatively normally, but can beat irregularly and put these individuals at risk of sudden death whe
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Contact: Karen Honey
press_releases@the-jci.org
212-342-4159
Journal of Clinical Investigation
24-Aug-2006


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