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Calcium Kicks

By Richard P. Grant Calcium Kicks Medi-Mation ltd / Photo researchers inc. The paper M.D. Fuller et al., “Molecular mechanism of calcium channel regulation in the fight-or-flight response,” Sci Signal, 3:ra70, 2010. Free F1000 Evaluation The finding Pounding heart, tight muscles, and rapid breathing are all familiar effects of the “fight or flight” response. Adrenaline receptors turn on protein kinase A (PKA), which opens ca

By | March 1, 2011

Calcium Kicks

Medi-Mation ltd / Photo researchers inc.

The paper

M.D. Fuller et al., “Molecular mechanism of calcium channel regulation in the fight-or-flight response,” Sci Signal, 3:ra70, 2010. Free F1000 Evaluation

The finding

Pounding heart, tight muscles, and rapid breathing are all familiar effects of the “fight or flight” response. Adrenaline receptors turn on protein kinase A (PKA), which opens calcium channels in muscle tissue, tensing the body for action. But which residues PKA phosphorylates to release a stopper mechanism within the channel was a 25-year-old mystery—until William Catterall and colleagues from the University of Washington in Seattle painstakingly worked out the details.

The mystery

The whole field was stumped, says Catterall: “It was an embarrassment we were all sweeping under the rug.” His lab tried to put the complex together in transfected cells, but they couldn’t get it to work. “It was a lot of frustration for multiple people in the lab,” he says.

The key

Then they had the idea to reduce the amount of a critical component. PKA is anchored to the membrane via a protein called AKAP. Catterall and colleagues noticed that too much free AKAP prevented the PKA bound to AKAP from reaching the channel. Once they reduced the amount they were putting into the cells, PKA was able to phosphorylate the channel and release the stopper mechanism.

The disease

Cracking this problem has now made it possible to study the regulation of calcium channels in normal heart function, and to ask if it’s impaired in heart failure. Catterall’s lab has just started doing those experiments. “We’re optimistic we will learn something interesting,” he says.

F1000 evaluators: G. Zamponi (Univ of Calgary)N. Dascal (Tel Aviv Univ)A. Dolphin (Univ Col London)

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Comments

Avatar of: anonymous poster

anonymous poster

Posts: 1

March 21, 2011

There are multiple AKAPs that are quite divergent in their signaling context. The specific AKAP in Dr. Catterall's paper was AKAP15. Other AKAPs do different things.

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