One of the most fascinating aspects of biology is the fact that components, many of which can not function on their own, when combined form something as complex and multifunctional as a living being. This prompts the thought that a component that shows one behavior on its own may show additional or completely new behaviors when part of a system. This is the basic thought for the field of systems biology, where experiences from engineering have been applied to biological systems in order to gain a deeper insight on how living things work. 

One system that has not yet been properly explained from reductionistic experiments is the β-adrenergic receptor signaling pathway. 

The β-adrenergic receptors belong to the class of G-protein coupled receptors (GPCRs). They exist in three different types of which two are common in the heart: β1 and β2, with β1 being by far most abundant. Known agonists for the receptors are for example isoprenaline (ISO) and the catecholamines adrenalin and noradrenalin.

From the receptor, the signal is transmitted through the signaling proteins Gs and Gi to adenylyl cyclase, which triggers production of cAMP. cAMP elicits contraction of the cells, but it also activates the kinases GRK and PKA which phosphorylates the receptor and regulates breakdown of cAMP in a negative feedback loop.

When the β-adrenergic receptor is first stimulated by an agonist, the cAMP concentration or the force of the muscle contraction displays a peak, where the levels first rises considerably and then rapidly falls again to a new steady state. This peak effect is typical of a negative feedback loop. Biologically it is thought to be mediated by phosphorylation of the receptor through the kinases activated by cAMP. The duration of the desensitisation can be measured by a second activation only shortly after the first activation, when the response from the system will be much subdued. 

In patients with heart failure the desensitisation is stronger and often become chronic as the receptors get internalized and downregulated. In the fetal heart the opposite is true, they seem immune to the desensitisation and is often sensitised by receptor activation.

What are the mechanisms behind the fetal lack of desensitization? This question is interesting enough on its own from a developmental perspective, but could knowledge gained from it also be used to help people with cardiac dysfunction?