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 Welcome to the Nichols lab, where ion
channels come to play! Look here to contact members of the lab and
learn about what projects we have going on at the moment. Please feel
free to contact any one of us for more information.
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Recent Projects:
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The Bionic Mouse
Mice lacking glucokinase in the pancreas normally never live beyond a
few days. The white mouse in the picture lacks glucokinase, but also
lacks KATP channels. For this reason it bypasses the need for glucose
metabolism in insulin secretion. It remains small and unhealthy but -
critically - it can survive. (see Remedi et al. 2005 Diabetes 54,
2925–2931).
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Seeing the ECG in 3-D
Optical mapping of electrical activity in a living mouse heart reveals
the action potential over the whole surface. These experiments have
revealed regional specificity of KATP structure and function, with a
previously unknown distinction between atria and ventricles. Such
regional differences may be critical in the cardiac response to ischemia.
(see Glukhov et al. 2009 J.M.C.C., in press).
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A channel to Diabetes
Islets from normal mouse pancreas contain lots of insulin that is
released to maintain blood glucose at normal levels. Mice – and people –
that express overactive potassium channels in the pancreas suffer
neonatal diabetes. The mouse model reveals complex secondary changes,
including unexpected disappearance of insulin and glucagons from the
islets. (see Remedi et al. 2009 Cell Metabolism, 9, 140-51).
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The Electronic Transducer of Metabolism
Nucleotide interaction with the nucleotide binding folds (NBFs) of the
sulfonylurea receptor is the essential link between cell metabolism and
activation of KATP channels. The structure of bacterial NBFs indicates an
obligate dimeric structure and molecuaklr modeling of SUR NBFs is
consistent. (see Masia et al. J Biol Chem. 283, 30322-9).
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The Ultimate Pore Blocker
In blocking K channels, spermine binds very deeply within the Kir
channel pore, so deeply that it moves more charge than it carries through
the electrical field. Molecular modeling suggests it can snake all the
way into the selectivity filter, pushing K ions through the pore ahead of
it. (see Kurata et al. 2004 J. Gen. Physiol. 124, 541-554).
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