Cl
- transporters 
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Research
The maintenance of the ionic content of cells and their environment is vital
to life. We are interested in the structural, biochemical and genetic mechanisms
involved in the regulation of ion transport and signaling by cells. Three types
of molecules are studied: ion channels, electroneutral transporters of cations
and anions, and divalent mineral sensors. We utilize molecular-genetic, biochemical,
pharmacological and physiological approaches to study the function, regulation
and structure of these proteins.
ATP-sensitive and ATP regulated
potassium channels
Movement
of ions through channels is governed by conformational changes
resulting
in channel opening or closing, also referred
to as gating. Ion channels have evolved an array of gating sensors.
We study how nucleotides and protons gate inwardly rectifying K
channels. We had cloned the initial member of this inward-rectifier
channel family in 1993. These K channels play vital roles in kidney,
heart, vascular smooth muscle, and pancreatic beta-cells and loss
of function mutations result in severe renal, cardiovascular, pancreatic
and CNS disorders.
Lie-qi Tang, Ke
Dong, Gordon MacGregor, Qiang
Leng, Anthony O'Connell
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G-protein coupled ion-sensors
Calcium
and certain other nutrients (amino acids and polyamines) can function
as extracellular signaling molecules or ìfirst messengersî by
activating a novel G protein-coupled receptor that we cloned in 1993.
This receptor provides the mechanism for sensing extracellular calcium
and transferring this information for regulation of the function
of many different types of cells. We are studying the roles of this
sensor in epithelial ion and fluid transport, proliferation and differentiation.
This receptor plays important roles in maintaining intestinal ìhealthî and
reducing the risk of colon cancer.
Sam Cheng, Alexandra Buschmann
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Sodium/Potassium coupled chloride transporters
Electroneutral
cation-coupled chloride transporters are crucial to chloride
absorptive and secretory epithelia, cell
volume regulation and the setting of intracellular chloride in
excitability in neurons. We cloned some of the members of this
family and study how they are regulated by ions, diuretics and
cytosolic second messengers.
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