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Channeling the heart’s pace

The heart’s regular rhythm is crucial to the delivery of oxygenated blood and nutrients to all the body’s organs.

OCTOBER 19, 2013 22:32

The heart’s regular rhythm is crucial to the delivery of oxygenated blood and nutrients to all the body’s organs. It is regulated by a bundle of cells called “the pacemaker,” which use electrical signals to set the pace of the heart. Dysfunction in this mechanism can lead to an irregular heartbeat, known as arrhythmia, and often necessitates the implantation of an artificial pacemaker.

Previously, scientists found that many cases of inherited arrhythmias originating in the pacemaker could be attributed to functional defects in the channels responsible for the flow of sodium and calcium.

Now Prof. Bernard Attali of Tel Aviv University’s Sackler Faculty of Medicine and his fellow researchers have discovered a previously unidentified potassium channel in the cardiac pacemaker that helps regulate the heartbeat. He hypothesizes that some cases of unexplained arrhythmia could be traced back to irregularities in this channel.

Developing therapies to target this potassium channel could be a significant step towards circumventing artificial pacemakers in favor of biological options, says Attali, whose research was recently published in the journal PNAS.

To further investigate the workings of the biological pacemaker, Attali and colleagues turned to embryonic stem cells isolated from human subjects. Once coaxed into differentiating into cardiac tissue, these cells began to beat automatically, like a small human heart. While observing and recording the cells’ electrical activity, researchers discovered the existence of a new channel in the pacemaker. Facilitating the flow of potassium from the pacemaker cells, this channel triggers the repolarization of the cells – returning the cell membrane from a “beating” to a “resting” state – and automatically renews or “restarts” the cycling of the heart.

Since discovering this channel in the embryonic heart, the researchers have shown that it exists in the adult heart as well. This finding deepens medicine’s understanding of the heart’s pacemaker function, which has been the subject of scientific research for over a century.

The next step was to screen for mutations in the gene encoding the potassium channel, a process already underway at the TAU-affiliated Sheba Medical Center.

“We would like to understand if there are genetic diseases linked to this channel,” such as a previously unknown cause of arrhythmia, explains Attali. If a mutation is found, researchers can begin the hunt for drug compounds, which target this channel. The ultimate goal, he adds, is to be able to treat heart arrhythmias biologically by altering the properties of the pacemaker bundle, rather than relying on a man-made electric pacemaker.

One possible solution could be transplanting healthy pacemaker cells – developed from a patient’s own stem cells – to replace dysfunctional cells and restore proper heart rhythm. This method would circumvent a common risk of the body rejecting a mechanical transplant.

BALTIMORE-HAIFA PARTNERSHIP The strong medical-research partnership with Johns Hopkins University of Baltimore, initiated over a decade ago by Prof. Rafi Beyar, director-general of Rambam Medical Center in Haifa, was reinforced recently. A Johns Hopkins presidential delegation came to Rambam and to Technion’s Faculty of Medicine to discuss “Frontiers in the Biomedical Sciences.”

The Johns Hopkins University – Technion Collaboration Program was established in April 2000 to promote cooperation in the fields of bioengineering and the biomedical sciences. The project aims to develop new technologies in the rapidly evolving field of cardiovascular medicine and other disciplines and to establish industrial relationships in order to make these technologies commercially available to patients.

Johns Hopkins president Prof. Ronald Daniels brought a select group of his physician-researchers to Rambam and to the Technion’s Rappaport Faculty of Medicine for a symposium entitled “Frontiers in the Biomedical Sciences.”

The guests were welcomed by Technion president Prof. Peretz Lavie, the Technion medical faculty’s dean Prof. Eliezer Shalev and Beyar.

Daniels spoke of the “intellectual excitement characterizing the relationship despite the painful moment in which it was hatched.” He was referring to the fact that the first meeting of the American and Israeli researcher partners, scheduled for November 2000 at Rambam, was postponed by the outbreak of the first intifada, and that it was eventually held in Baltimore on September 11, 2001, when terrorists toppled Manhattan’s World Trade Center and killed thousands.

LIMIT TODDLERS’ TV WATCHING Try to minimize your toddler’s TV watching if you want them to do well in kindergarten, according to recommendations by the American Academy of Pediatrics.

An extra hour beyond its guidelines reduces toddlers’ success in kindergarten, said Prof. Linda Pagani of the University of Montreal and the nearby CHU Sainte-Justine children’s hospital.

Every hourly increase in daily television watching at 29 months of age is associated with diminished vocabulary and math skills, classroom engagement (which is largely determined by attention skills), victimization by classmates, and physical prowess, Pagani said.

“This is the first time ever that a stringently controlled associational birth cohort study has looked at and found a relationship between too much toddler screen time and kindergarten risks for poor motor skills and psychosocial difficulties, like victimization by classmates,” Pagani continued. “These findings suggest the need for better parental awareness and compliance with existing viewing recommendations put forth by the AAP. The AAP discourages watching television during infancy and recommends not more than two hours per day beyond age two. It seems that every extra hour beyond that has a remarkably negative influence.”

Much of the research on school readiness has focused on how kindergarten characteristics predict later success, the Canadian researcher said. “Kindergarten entry characteristics predict long-term psychosocial adjustment and economic characteristics like income and academic attainment. A total of 991 Quebecois girls and 1,006 boys, and their parents, participated in the study as part of the Quebec Longitudinal Study of Child Development.

The study, noted Pagani, looks only at the most common form of screen time, which is in the home. However, it may be a low estimate because many childcare settings use television as an activity during care giving.

“Because of kindergarten’s power to predict future productivity, the identification of modifiable factors that foretell not being ready for the transition to formal schooling represents an important goal for a productive society.”

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