5.27.2009

Oh its there trust me, cAMP is everywhere, you just can't see it.

cAMP is a VERY important molecule. Here it is: 
This thing is arguably as important as ATP its more hot-headed relative - but look at the trans-phosphodiester bond between C3 and C4, that thing creates significant instability. And so we learned that cAMP binds PKA (protein kinase A) and other intracellular proteins activating them motivating them regulating them. If ATP is your rich uncle that pays for everything, cAMP is the unstable motivational speaker of the subcellular world, it binds inactive enzymes and "animates" them. If you are like me and drink coffee, you would care about all this because the psychostimulant caffeine inhibits phosphodiesterase, the enzyme that breaks the 4' phosphoester bond in cAMP. Thus caffeine indirectly raises cAMP inside the cell, something called disinhibition. 

Here is a new paper out this month.

There was no way to visualize intracellular cAMP for all of time until someone figured out how to show the molecule bound to PKA. The problem with this technique is that it is slow, takes forever, and cannot capture the momentary changes in cAMP that happen during normal physiology. Until now...

Epac is a cAMP exchange factor, like GAPs and GEFs. This is what they did. They took an adeno virus and added Epac-1 (protein holds cAMP), and also tagged it with YFP (yellow fluorescent protein). Then took specific parts of the brainstem known as pre-Botzinger complex neurons that are very sensitive to cAMP (the mediate respiration). They changed the cellular environment a whole bunch of time with different conditions and captured with on a microscope. 

Here is intracellular cAMP 



Here there is the medulla on slice! How nice! NTS - nucleus of the solitary tract, yup there is CNXII hypoglossal right where is should be. I love neuroanatomy. Pretty neat finding, I bet this will be a lab technique that gets a lot of use.


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