May 2007 — Scientists have discovered how we put the brakes on a racing heartbeat.
Researchers at the University of Illinois at Chicago explain in the May
11 issue of Circulation Research how an enzyme acts on the heart’s
pacemaker to slow the rapid beating of the heart’s "fight-or-flight"
reaction to adrenaline.
A single cell in the upper right chamber is responsible for setting
the pace of the beating heart, triggering its neighbor cells to beat.
In the human heart, one cell — the pacemaker cell — beats faster or
slower to induce a rhythmic heartbeat that varies to increase or
decrease the blood flow to the body as we eat, sleep or exercise.
"Disturbances of pacemaker control are common in heart diseases.
When the heartbeat becomes non-rhythmic and chaotic, it can result in
fatal arrhythmias and stroke," said R. John Solaro, UIC distinguished
university professor and principal investigator of the study.
Current treatment of arrhythmia requires destruction of tissue
surrounding a chaotic pacemaker, followed by insertion of a mechanical
pacemaker that can regulate the heartbeat. "Understanding the molecular
regulation of the heart’s pacemaker opens the possibility of less
drastic treatment options, including drug interventions," said Solaro,
who is also director of the center for cardiovascular research and head
of physiology and biophysics at UIC.
Solaro worked with Yunbo Ke, UIC research assistant professor of
physiology and biophysics and first author of the paper, and colleagues
in England at Oxford and Manchester on characterizing and isolating the
The UIC researchers demonstrated that an enzyme called Pak 1,
present in high concentrations in the heart, signals depression in the
action of adrenaline and adrenaline-like chemicals on the pacemaker
cell, playing an important role in slowing down the heart rate. "The
enzyme works through calcium and potassium channels that we know to be
key players in the generation and regulation of the pacemaker
activity," said Ke.
"Although adrenaline and other mechanisms that accelerate the heart
rate have been well studied, mechanisms that might act as a brake are
poorly understood," said Solaro.
"Identification of this previously unknown molecular mechanism for
slowing the heartbeat may offer new avenues of diagnosis, drug design
and treatment of many common heart diseases," said Solaro.
"Further, now that we know something of how this enzyme works in the
pacemaker cell, we may discover it is involved in the regulation of
other processes, particularly in the brain, where it is also highly
expressed," added Ke.
Other contributors include Dr. Derek Tarrar, Thomas Collins, Stevan
Rakovic, Paul Mattick and Michiko Yamasaki at Oxford; Dr. Ming Lei at
the University of Manchester; and Mark Brodie at UIC.
The study was supported by grants from the National Institutes of Health, the Wellcome Trust and the British Heart Foundation.