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Increased Calcium Sensitivity In The Heart Can Make For An Irregular Heartbeat

Date:
November 28, 2008
Source:
Journal of Clinical Investigation
Summary:
New mouse studies, by Björn C. Knollmann and colleagues, at Vanderbilt Medical Center, Nashville, have uncovered a potential new molecular mechanism to explain why some individuals suffer irregular heartbeats that can cause sudden death. The results suggest a potential new target for drugs that would be beneficial to those at risk.
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New mouse studies, by Björn C. Knollmann and colleagues, at Vanderbilt Medical Center, Nashville, have uncovered a potential new molecular mechanism to explain why some individuals suffer irregular heartbeats that can cause sudden death. The results suggest a potential new target for drugs that would be beneficial to those at risk.

Sudden cardiac death caused by irregular heartbeats (cardiac arrhythmias) is responsible for 10% of all deaths in the US. In some individuals anatomical abnormalities in the heart (such as hypertrophic cardiomyopathy, a disease of the muscle of the heart characterized by a portion of the muscle being thickened) increase the risk of irregular heartbeats and sudden death.

In the study, mice expressing mutant forms of the protein troponin T that cause hypertrophic cardiomyopathy in humans were found to have an increased risk of irregular heartbeats. Detailed analysis indicated that the enhanced susceptibility to irregular heartbeats was a result of increased sensitivity of a key component of the heart contractile units (specifically the myofilaments) to Ca2+.

As the drug blebbistatin, which decreases the sensitivity of myofilaments to Ca2+, provided the mice with substantial protection from irregular heartbeats, the authors suggest that normalizing myofilament Ca2+sensitivity in individuals with hypertrophic cardiomyopathy might help protect them from irregular heartbeats and sudden death.

In an accompanying commentary, Céline Fiset and Wayne R. Giles provide insight into the complexities of the new data, highlighting their significance.


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The above post is reprinted from materials provided by Journal of Clinical Investigation. Note: Materials may be edited for content and length.


Journal References:

  1. Baudenbacher et al. Myofilament Ca2+ sensitization causes susceptibility to cardiac arrhythmia in mice. Journal of Clinical Investigation, 2008; DOI: 10.1172/JCI36642
  2. Fiset et al. Cardiac troponin T mutations promote life-threatening arrhythmias. Journal of Clinical Investigation, 2008; DOI: 10.1172/JCI37787

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Journal of Clinical Investigation. "Increased Calcium Sensitivity In The Heart Can Make For An Irregular Heartbeat." ScienceDaily. ScienceDaily, 28 November 2008. <www.sciencedaily.com/releases/2008/11/081120173129.htm>.
Journal of Clinical Investigation. (2008, November 28). Increased Calcium Sensitivity In The Heart Can Make For An Irregular Heartbeat. ScienceDaily. Retrieved June 30, 2015 from www.sciencedaily.com/releases/2008/11/081120173129.htm
Journal of Clinical Investigation. "Increased Calcium Sensitivity In The Heart Can Make For An Irregular Heartbeat." ScienceDaily. www.sciencedaily.com/releases/2008/11/081120173129.htm (accessed June 30, 2015).

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