Source: The Salk Institute For Biological Studies
http://www.sciencedaily.com/releases/1999/01/990113075613.htm
Zinc Found To Be Integral Part Of Brain Communication Channels
LA JOLLA, CALIF. January 6, 1999 -- Zinc has long been recognized as an
essential trace element, and a current study led by Salk Institute
investigators shows it to be an integral part of ion channels,
structures that regulate communication among nerve cells.
The study, which appears in the current issue of Nature Structural
Biology, may explain why zinc deficiency has been linked to cognitive
impairment.
"We don't know yet what zinc is doing, but it is definitely a component
in these essential structures," said Senyon Choe, an assistant professor
at The Salk Institute for Biological Studies and senior author on the
study. "And it was surprising--at first we tried to disregard it,
thinking it must be a contaminant, but, of course as you try to disprove
it, it keeps coming back."
Ion channels are important "gatekeepers" that regulate the way ions such
as calcium and potassium flow into and out of cells. Their flux is
necessary for important neuronal processes. Calcium streams into brain
cells and helps to initiate changes that accompany learning.
Abnormalities in potassium channels have been found in some epileptics
and in persons with both insulin-resistance and mobility disorders.
In the current study, Choe and his colleagues used X-ray crystallography
to resolve the structures of four potassium channels from the sea slug
Aplysia. The channels, called Shaw, Shab, Shal and Shaker, represent the
four classes of potassium channels found in all higher organisms,
including humans. With the exception of Shaker, all of the channels
contained four zinc atoms in analogous positions.
"Each channel resembles a funnel," said Choe, "and the zinc elements
ring the end that empties into the cell's interior."
Neuroscientists have known for decades that dyes that bind to zinc stain
brain cells in unique patterns, indicating that zinc should have a role
in brain function and studies have shown that zinc can enhance learning
in undernourished children. The nature of zinc's organization in the
brain, however, had been unclear.
"Now we know that zinc is embedded within structures that are absolutely
critical for nerve cell activity," said Choe. "Furthermore, the amino
acids that cradle the zinc atoms are completely conserved among the
three classes of channels, telling us that during evolution there has
been selective pressure to keep that zinc in place."
All four kinds of Aplysia potassium channels studied by Choe and
colleagues have analogs in the human nervous system, so the
investigators believe that their studies of zinc's role in Aplysia
channel function are directly relevant to understanding its function in
the human brain.
First author of the study, titled "Zn2+-binding and molecular
determinants of tetramerization in voltage-gated K+ channels," is
Kathryn Bixby, currently at the University of California, San Diego.
Other Salk authors include Andreas Kreusch, a postdoctoral researcher in
Choe's laboratory and Max Nanao, who is also a graduate student at the
University of California, San Diego. The study was done in collaboration
with N. Vivienne Shen and Paul J. Pffafinger at Baylor College of
Medicine and Henry Bellamy at the Stanford Synchroton Radiation
Laboratory. The work was supported by the National Institutes of
Health and the American Heart Association.
--
Judith Richards, London, Ontario, Canada
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