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Rare disease provides clues about enzyme role in arrhythmias
Date:12/11/2008

art muscle then takes longer to recharge between beats and can lead to irregular heartbeat.

"The findings raise the possibility that CaM kinase II is a 'missing link' that connects this calcium channel mutation to arrhythmia and possibly other problems, such as autism," said Anderson, who also holds the Potter-Lambert Chair in Cardiology and is a member of the University of Iowa Heart and Vascular Center. "Our findings add more evidence that by acting on CaM kinase II, you could directly affect pathways that cause unwanted developmental and neurological changes."

"In contrast to sodium channels or potassium channels, there are very few diseases that cause mutations in calcium channels. Experts believe calcium is too important to 'futz' around with, perhaps accounting for the very severe nature and early death associated with patients with Timothy syndrome," Anderson added.

While previous researchers had observed defects in calcium channels in other cells, those cells did not have the coordinated electrical function of a heart. The University of Iowa team, using the expertise of Bill Thiel, Ph.D., postdoctoral trainee, and Peter Mohler, Ph.D., associate professor of internal medicine and a Pew Scholar, developed and assessed a cellular model to more clearly reveal the function that helps drive heartbeats.

"By studying this mutant channel in an adult rat heart cell that had all the proteins and machinery of a normal heart cell, we obtained a much more complete picture of how the disease works," Anderson said. "When CaM kinase II was turned on in the cellular model, the activation was responsible for the heart rhythm problems. In contrast, when we inhibited the enzyme using a peptide, the disease features healed, the electrical oscillations resolved and the action potential was corrected."

Even though the calcium channel defect in Timothy syndrome is relatively tiny, the defect seriously affects the ability of the heart to
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Contact: Becky Soglin
becky-soglin@uiowa.edu
319-335-6660
University of Iowa
Source:Eurekalert

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