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

A University of Iowa study provides insight into a calcium-sensing enzyme already known to play a role in irregular heartbeats and other critical functions. The researchers showed that the enzyme, calmodulin kinase II (CaM kinase II), contributes to arrhythmia in an extremely rare disease called Timothy syndrome and that inhibiting the enzyme prevents irregular heartbeats.

The findings, which involved a new cellular model, could help with developing treatments for irregular heartbeat in people with this syndrome as well as in the general population. There also could be implications for understanding other conditions such as autism. The study results were published online Nov. 10 by the journal Circulation.

Timothy syndrome has been reported in only about 20 people worldwide. In addition to causing an irregular heartbeat, Timothy syndrome can cause a malformed heart, autism and other nervous system problems. Timothy Syndrome is a type of long QT syndrome, which can cause sudden death in people with normal-appearing hearts.

"We focused on the multisystem disease Timothy syndrome and showed that its hallmark fatal heart disease, which typically is fatal by age 3, involves activation of the enzyme CaM kinase II. We also showed that inhibiting this enzyme prevented irregular heartbeats in adult rat heart cells engineered to express the Timothy syndrome disease gene," said study author Mark Anderson, M.D., Ph.D., professor of internal medicine and molecular physiology and biophysics at the University of Iowa Carver College of Medicine.

CaM kinase II was already known to play a role in arrhythmias but the study helps uncover the enzyme's interplay with calcium channels, which provide the main way for calcium to enter heart cells. Calcium is needed to trigger each heartbeat and to help regulate cell survival, metabolism and gene transcription. In Timothy syndrome, a mutation causes the calcium channel to be malformed. The he
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Contact: Becky Soglin
becky-soglin@uiowa.edu
319-335-6660
University of Iowa
Source:Eurekalert

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