http://www.sciencedaily.com/releases/2005/04/050418094430.htm

Source:  
  Washington University School of Medicine

Date:  
  2005-04-18  
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Fat May Affect Electrical Impulses In Brain, Heart

April 14, 2005 -- Fatty molecules may modulate the electrical
characteristics of nerve and heart cells by regulating the properties of
key cell pores, according to research conducted at Washington University
School of Medicine in St. Louis.

The findings suggest a novel mechanism in which dietary fat can attach
directly to proteins that regulate bioelectricity. This can affect the
performance of nerve and heart cells, with potentially broad-ranging
health implications.

The researchers report in the April 26 issue of the Proceedings of the
National Academy of Sciences that the proteins in specific electrically
responsive cell pores--voltage-sensing potassium channels--can bind to
molecules of palmitate. Palmitate is a saturated fatty acid previously
linked to "hardening" of the arteries and obesity and is a common fat in
unhealthy diets.

"In effect, the attachment of palmitate makes these potassium channels,
called Kv1.1 channels, open more easily, and this can influence the
transmission of electrical impulses along nerve cells and the
contraction of heart muscle cells," says senior author Richard Gross,
M.D., Ph.D., professor of medicine, of chemistry and of molecular
biology and pharmacology and director of the Division of Bioorganic
Chemistry and Molecular Pharmacology.

Potassium channels are among the most important cell channels used for
propagating electrical signals in nerve and heart muscle. Their protein
units form pores that permeate the outer wall or membrane of the cell
and selectively allow the passage of potassium ions, which are essential
components of cell signaling systems.

Like a meter that measures charge in a battery, a Kv1.1 channel senses
the amount of voltage between the interior and exterior of cells and can
open and close in response to voltage changes.

Because they are embedded in the cell membrane, Kv1.1 channels are
tightly surrounded by the fatty molecules of the membrane, which line up
next to each other to create a stable structure.

"We think the attached palmitate molecule causes a defect in the close,
regular packing of the membrane's fatty molecules around the Kv1.1
channel, because the palmitate has a different shape," Gross says. "This
shape loosens the membrane packing, changes the movement of the channel
protein and alters the voltage needed for it to open or close."

The researchers identified the specific site or amino acid in the Kv1.1
protein units that palmitate most often links to. They discovered that a
short sequence of amino acids on either side of the attachment site is
found in several other proteins as well, arguing for an evolutionarily
conserved function for this amino acid sequence.

Most strikingly, five of six amino acids adjacent to the attachment site
matched a site where palmitate is known to attach to CD36, an abundant
protein vital for moving fatty molecules through the membrane into
cells.

"When we see that molecules as widespread, as important and as different
from each other as CD36 and Kv1.1 are linked to palmitate at the same
sequence--that's nature sending us a message," Gross says. "It's
possible that this palmitate attachment site has been used throughout
evolution to fulfill functions involving fatty molecules."

Future investigations will seek to further characterize the electrical
properties conferred by the addition of palmitate to Kv1.1. The research
team will also begin studies with mice to determine the effects of
dietary fats on palmitate attachment and the electrical characteristics
of cells.

"We want to find out if a connection exists between dietary fats, the
attachment of palmitate to proteins and health," Gross says. "In obesity
or in cellular lipotoxicity, you exceed cells' capacity to handle fatty
acids. Accumulation of fatty acids can lead to an increase in
alterations like palmitate attachment, not only in Kv1.1, but in dozens
or even hundreds of other proteins. That possibly explains some of the
many types of damage that result from having too high of a fatty acid
burden."


###

Gubitosi-Klug RA, Mancuso DJ, Gross RW. The human Kv1.1 channel is
palmitoylated, modulating voltage sensing: Identification of a
palmitoylation consensus sequence. Proceedings of the National Academy
of Sciences. 2005;102(17): 5964-5968.

Funding from the National Institutes of Health supported this research.

View online:
http://news-info.wustl.edu/news/page/normal/5098.html?emailID=5077

Washington University School of Medicine's full-time and volunteer
faculty physicians also are the medical staff of Barnes-Jewish and St.
Louis Children's hospitals. The School of Medicine is one of the leading
medical research, teaching and patient care institutions in the nation,
currently ranked third in the nation by U.S. News & World Report.
Through its affiliations with Barnes-Jewish and St. Louis Children's
hospitals, the School of Medicine is linked to BJC HealthCare.

Editor's Note: The original news release can be found here.
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This story has been adapted from a news release issued by Washington
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This is the abstract.

Naunyn Schmiedebergs Arch Pharmacol. 2005 Apr 15; [Epub ahead of print]
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Antiarrhythmic and electrophysiological effects of long-chain omega-3
polyunsaturated fatty acids.

Dhein S, Michaelis B, Mohr FW.

Clinic for Cardiac Surgery, University of Leipzig, Heart Center,
Struempellstrasse 39, 04289, Leipzig, Germany, dhes@medizin.uni-leipzig.de.

Recent studies indicate that a diet enriched in omega-3 polyunsaturated
fatty acids may prevent sudden cardiac death. The goal of the present study
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velocity V(T). Anisotropy was not significantly changed. EPA and ALA did not
exhibit a systematic effect on V(L) or V(T). These results clearly
demonstrate that DHA, EPA, and ALA exhibit direct electrophysiological
effects with different profiles. PMID: 15834553

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstra
ct&list_uids=15834553