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Colin Nichols Lab

 

 

 

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.

 

Recent Projects:

 

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).


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).


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).

 


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).

 

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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