Cardiac arrhythmias leading to sudden cardiac death (SCD) cause 10 percent of all deaths in the USA. Hypertrophic cardiomyopathy (HCM) is a condition that is well known for causing SCD in young athletes, but it affects people of all ages. The characteristics of HCM include thickening of the heart muscle tissue, mitral valve defects and muscle cell misalignment. Since SCD can occur in the absence of heart structure abnormalities, Baudenbacher et al. investigated the possibility that HCM-linked mutations in the contractile protein troponin T play a role in Ca2+ sensitivity and arrhythmia susceptibility. When expressed in mice, these mutations changed the Ca2+ sensitivity of heart muscle fibers. Further, the severity of the mutation was directly proportional to the risk of developing heart arrhythmia. Additional tests using pharmacological manipulation of Ca2+ sensitivity support this novel arrhythmia mechanism and highlight the potential for a new type of anti-arrhythmia intervention.
Baudenbacher F., Schober T., Pinto J. R., Sidorov V. Y., Hilliard F., Solaro R. J., Potter J. D., Knollmann B. C. (2008). Myofilament Ca2+ sensitization causes susceptibility to cardiac arrhythmia in mice. J. Clin. Invest. 118, 3893– 3903.
