A worldwide group of scientists has created an infectious prion disease in a mouse model, in a step that may help unravel the mystery of this progressive disease that affects the nervous system in humans and animals. The research team, including Christina J. Sigurdson, D.V.M., Ph.D., assistant professor of pathology at the University of California,
Full Post: Scientists create infectious prion disease in mouse model
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 heart 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 keep a regular beat, Anderson said.
“The defect causes the channel to close too slowly, and this in turn amplifies CaM kinase II, which in turn can cause disease,” he said. “You can’t completely block calcium channels because you need some function to initiate heartbeats. Ideally, we would find a way to allow the defective channel to operate but without allowing the CaM kinase II to be over activated.”
http://www.uiowa.edu/
--------------------------------------------------------------------------------------------
Related Posts:
Treating a common heart rhythm disorder by burning heart tissue with a catheter works dramatically better than drug treatments, a major international study has found. One year after undergoing a treatment called catheter ablation, 75 percent of patients with an irregular heartbeat called atrial fibrillation were free of symptoms. By comparison, only 21 percent of
Full Post: Catheter ablation works better than drugs for heart rhythm disorder
A Queen’s University study sheds new light on the way one of our cell enzymes, implicated in causing tissue damage after heart attacks and strokes, is normally kept under control. Led by Biochemistry professor Peter Davies, the research team’s discovery will be useful in developing new drug treatments that can aid recovery in stroke and
Full Post: Enzyme discovery may lead to better heart and stroke treatments
A compound designed to prevent chest pains in heart patients has shown promising results in animal studies, say scientists. In the second issue of the British Journal of Pharmacology to be published by Wiley-Blackwell, researchers from the Centre de Recherche Pierre Fabre in France, show that the novel compound F15845 has anti-angina activity and can
Full Post: Novel compound F15845 shows promise for angina
Brain researchers at the University of Oslo in Norway have penetrated deeply into the innermost secrets of the brain to find out how brain cells can survive a stroke. Strokes are usually caused by occlusion of one of the blood vessels in the brain. When blood is prevented from supplying vital oxygen and energy to
Full Post: Researcers discover how brain cells can survive a stroke
A discovery by Canada-U.S. biophysicists will improve the understanding of ion channels, akin to little ‘nano-machines’ or ‘nano-valves’ in our body, which when they malfunction can cause genetic illnesses that attack muscles, the central nervous system and the heart. As reported in the current issue of the Proceedings of the National Academy of Sciences (
Full Post: New understanding of ion channels in the body --------------------------------------------------------------------------------------------
