FOR IMMEDIATE RELEASE
Contact:
Donna Krupa
703.527.7357 (direct
dial)
703.967.2751 (cell) or
djkrupa1@aol.com
AMERICAN PHYSIOLOGICAL
SOCIETY (APS)
CONVENES INTERNATIONAL GATHERING OF EXPERTS AT FALL CONFERENCE I
Featured research findings include
the first molecular demonstration of the presence of Na+/Ca2+
exchangers in olfactory tissue; the K+-dependent Na/Ca exchanger
isoforms expressed in brain; observations about cyclosporin A in the
treatment of hypertrophy and heart failure; and
cardiac Na+/Ca2+ exchange in neonates vs.
adults.
October 10, 2001 - Bethesda, MD -- The 4th
International Conference on Sodium-Calcium Exchange:
Cellular and Molecular Physiology of Sodium-Calcium Exchange, will
convene October 10-14, 2001 in Banff, Alberta, Canada. This gathering of
more than 100 international and interdisciplinary experts is being sponsored
by the American Physiological Society (APS).
Background
The physiological functions of vision, secretion and
cardiac contractility are strongly dependent on sodium-calcium (Na+-Ca2+)
exchange activity, according to the proceedings of the last NCX conference
held in 1995 and published by the New York Academy of Sciences (Volume 779,
p. xiii). Research efforts stem from the realization that “In many cell
types, sodium-calcium exchange is the primary mechanism of calcium
extrusion, and small changes of sodium-calcium exchange activity have large
effects on cell function. In heart and in brain, sodium-calcium exchange
activity likely becomes pivotal in pathological settings with possible
outcomes of calcium overload, altered electrical activity and ultimately
cell death.” (p. xiii).
Since the Na+-Ca2+ exchanger (NCX)
was first identified in heart muscle in 1968-1969 (p.7), it has been
identified in virtually every tissue examined as well as in a variety of
species, including human, dog, squid and fruitfly. The 1990 cloning of NCX1
from heart led to the discovery of different NCX isoforms in kidney, brain
and vascular smooth muscle, as well as to the cloning of two new NCX genes,
NCX2 and NCX3 from mammalian brain and skeletal muscle. A
separate sub-family of Na+/Ca2+ exchangers, NCKX, was
also identified in eye, brain and smooth muscle, that depend upon and
transport potassium (K+) as well as Na+ and Ca2+.
These data have provided further avenues for scientific exploration for the
benefit of human health.
Conference and Featured Topics
This year’s conference focuses on Na+/Ca2+
exchange at the cellular and molecular level. The depth and breadth of the
presentations is solid evidence of the advances that have been made since
the last meeting, held in 1995 in Woods Hole, MA.
The following presentations are among the highlights of
the invited presentations and poster sessions being conducted during the
gathering:
Sodium Calcium Exchangers in Olfactory Tissue
Olfactory marker protein (OMP)
is a 19-kDa cytoplasmic protein selectively expressed in mature olfactory
sensory neurons from fish to humans. OMP-null mice show delays in the onset
and recovery phases of electro-olfactograms following odorant stimulation
when compared to controls. As defective Ca2+ regulation could be
responsible for these effects, Dr. Dan Schulze Department of Microbio-Immunology
and Dr. Frank Margolis, Department of Anatomy/Neurobiology and their
colleagues at the University of Maryland examined the interaction of OMP and
the Na+/Ca2+ exchanger in Xenopus oocytes and
observed an OMP concentration-dependent decrease in Na+/Ca2+
exchanger activity. Their analyses provides the first molecular
demonstration of the presence of Na+/Ca2+ exchangers
in olfactory tissue and their interaction with OMP. Dr. Schulze will discuss
in detail at the meeting, provide the first molecular demonstration of the
presence of Na+/Ca2+ exchangers in olfactory tissue
and their interaction with OMP.
The Brain and Functional Properties of the K+-Dependent Na+/Ca2+
Exchanger Isoforms
In the more than three
decades since it was first characterized, researchers have come to
appreciate that the Na+/Ca2+ exchanger molecule plays
a critical role in Ca2+ homeostasis in neurons. Genome analysis
indicates that Na+/Ca2+ exchangers are a superfamily
encoded by seven different genes that are divided into two groups: the Na+/Ca2+
exchangers (NCX; SLC8) and the Na+/Ca2++K+
exchangers (NCKX; SLC24). The unique role that each exchanger gene
plays in neuronal calcium homeostasis is being investigated by Dr. Jonathan
Lytton and his colleagues at the Department of Biochemistry & Molecular
Biology, University of Calgary, Calgary, Alberta, Canada. Dr. Lytton will
present recent findings examining both the expression pattern and functional
properties of the K+-dependent Na+/Ca2+
exchanger isoforms expressed in the brain.
Na+/Ca2+
Exchanger Overexpression Impairs Contractility
In the failing human heart,
expression of sarcolemmal Na+/Ca2+ exchanger (NCX) is
increased. Because NCX can work in the forward and reversed mode, increased
expression could result in cellular calcium loss or gain. Correlative
analysis in failing human hearts indicates that NCX predominantly eliminates
calcium and contributes to reduced sarcoplasmic reticulum calcium load. To
test the concept, Professors Gerd Hasenfuss and W. Schillinger, of the
Department of Cardiology and Pneumology at the University of Goettingen,
Goettingen, Germany, examined the effect of NCX overexpression in isolated
myocytes. The results of their study show that overexpression of NCX causes
depression of contractile function similar to that observed in failing human
myocardium. This supports the hypothesis that upregulation of NCX can result
in myocardial failure.
Cyclosporin A, Hypertrophy and Heart Failure
Female homozygous transgenic
mice that overexpress NCX1 develop heart failure and premature death
following the first and second pregnancy. Earlier research has demonstrated
that treatment of cardiac hypertrophy in pressure-overloaded wild-type mice
with cyclosporin A (CSA; a calcineurin inhibitor), can prevent cardiac
hypertrophy and downregulation of NCX1 expression. To establish the
significance of NCX1 upregulation in cardiac hypertrophy, Susanne B.
Nicholas, MD, Ph.D., in the Department of Medicine at the University of
California, Los Angeles, investigated the effect of CSA on NCX1 expression
and development of cardiac hypertrophy in transverse aortic
constriction-induced cardiac hypertrophy in NCX1-overexpressing mice. Dr.
Nicholas will discuss her findings and expand upon her work on the
regulation of Na/Ca exchanger expression in cardiac hypertrophy during her
Saturday, October 13 presentation.
Cardiac
NCX in Neonates vs. Adults
When children, especially
newborns, are given gas anesthetics for surgical procedures, their hearts
slow down and beat more weakly while the anesthetics are being administered.
Usually, other drugs need to be given in the operating room to counteract
this side effect of anesthetics. A team of researchers has recently examined
whether such anesthetic effects on the newborn heart involve one of the
mechanisms that regulates calcium in cardiac muscle, which is very important
in determining the force with which the heart beats. Newborn hearts are
relatively more dependent on a process called sodium (Na+)-calcium
(Ca2+) exchange exchange (NCX) for calcium handling during
contraction and relaxation, compared to hearts of adults. Every time the
heart beats, NCX helps to bring calcium into the cardiac muscle during
contraction and helps to push calcium out of the muscle during relaxation.
Using an animal model, these investigators determined whether anesthetics
interfere more with NCX function in the neonatal heart, and thus cause more
cardiac depression during anesthesia.
The findings of the
investigation conducted by Y.S. Prakash, Ph.D., L.W. Hunter, Inanc Seckin,
and Gary C. Sieck, of the Department of Anesthesiology at the Mayo Clinic,
will be presented in detail by Dr. Prakash.
-end-
The American Physiological Society (APS)
is sponsoring this conference, the first of its two Fall conferences this
year. The APS was founded in 1887 to foster basic and applied science, much
of it relating to human health. The Bethesda, MD-based Society has more than
10,000 members and publishes 3,800 articles in its 14 peer-reviewed journals
each year.
***
Editor’s Note: To receive a copy of the abstracts, to interview speakers or
for more information, contact Donna Krupa at 703.527.7357(direct dial),
703.967.2751 (cell) or djkrupa1@aol.com.
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