Department of Regenerative Medicine and Cell biology

Research in Focus

Calmodulin Acts to Brake Calcium Release Events in the Heart

Contraction of cardiac muscle is controlled by intracellular Ca2+ concentration. The sarcoplasmic reticulm (SR) Ca2+ release channel, RyR2, plays a major role in elevating intracellular Ca2+ concentration. Mice expressing a mutant form of RyR2, not regulated by calmodulin, have severe cardiac hypertrophy and cardiomyocytes from the mutants display sustained global Ca2+ transients. Researchers in the Yamaguchi and Morad laboratories have measured elementary RyR2 Ca2+ release events (Ca2+ sparks) in RyR2 mutant and wildtype ventricular myocytes and found that the durations of individual sparks are greatly prolonged in the mutant cells. Their findings support a hypothesis that calmodulin plays a role as a "brake" of SR Ca2+ release, thereby preventing prolonged Ca2+ release and possible cardiac arrhythmogenesis. rif4
Time course of Ca2+ sparks. Top panel show original frames and the regions that were used to measure the sparks of fluorescence and the temporal course of recordings with confocal microscopy. Below are the representations of the fluoresence changes (ΔF/F0) and the temporal course of individual Ca2+ sparks for wild type (left) and mutant (right).

posted 9/28/2011

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