Image by M Machado and S Pantano
Prof Zaccolo explains their research and its significance below:
The primordial fight-or-flight response is a physiological reaction to stress. Under stress, the hormones adrenaline and noradrenaline trigger the production of a small signalling molecule, cAMP, that acts inside the cell to activate the appropriate reaction to the stressful situation. We developed a method, based on the use of fluorescent light, which allows us to see cAMP inside living cells. We have applied this technique to study the reaction of the heart to stress and we discovered a surprising feature of cAMP signals. We found that when adrenaline instructs the cardiac cells to generate cAMP, a multitude of different cAMP signals are generated. Each of these cAMP signals has a different function and is confined to a minuscule space within the cell, only a few millionths of a millimetre in size. We also found that in disease conditions, for example in heart failure, these tiny signals are disrupted.
We are very excited about our findings because they offer the opportunity to think about treatment of cardiac disease in a completely new perspective. Current drugs typically use a ‘blanket’ approach, their action occurs indiscriminately across the entire cell. If we understand how the tiny cAMP signals are generated in the heart - and we have already some good hints - we can target them individually and be more precise in the therapeutic intervention, increasing efficacy while minimising side effects.
Their paper "FRET biosensor uncovers cAMP nano-domains at β-adrenergic targets that dictate precise tuning of cardiac contractility" was published in Nature Communications.
The research published in this article was funded by the British Heart Foundation and the Oxford BHF CRE.
Read the full article here.