A new nanoscale scanning technique developed at Imperial College London could lead to better-designed beta-blockers to slow the development of heart failure, researchers believe.

The technique, called scanning ion conductance microscopy (SICM), generates a more detailed image of the surface of an individual heart muscle cell than could be achieved with conventional live microscopy.

In a study funded by the Wellcome Trust and the Leducq Foundation, researchers from the UK and Germany were able to examine fine structures such as the minute tubes (t-tubules) that carry electrical signals deep into the core of the heart muscle cell.

Using living cardiac muscle cells from healthy or failing rat hearts, the scientists combined SICM with new chemical probes that produce fluorescent signals on activation of beta1AR and beta2AR, the adrenergic receptors affecting heart function.

In heart failure, the researchers explained, hormones such as adrenaline are activated by the body in an attempt to stimulate a weak heart, but eventually cause further damage and deterioration. The beta1AR receptor for adrenaline strongly stimulates heart contraction and can also induce cell damage in the long term. The beta2AR receptor can slightly stimulate contraction but also has special protective properties.

In their study published in the journal Science, researchers from the National Heart and Lung Institute and the Division of Medicine at Imperial College London, as well as the Institute of Pharmacology and Toxicology and Rudolf-Virchow-Centre, University of Würzburg, Germany, found that in cells damaged by heart failure, the beta2AR receptors – which are normally anchored in the t-tubules – change location and move into the same space as the beta1AR receptors.

The researchers believe this change in the distribution of beta1AR and beta2AR receptors may affect their ability to protect cells and lead to more rapid degeneration of the failing heart.

Beta-blockers prevent adrenaline from acting on the heart cells by targeting the beta receptors. According to the researchers, the new findings enhance understanding of what happens to the two receptors in heart failure and could result in improved beta-blocker drugs. The research may eventually help to resolve the debate over whether it is better to block the beta2AR as well as the beta1AR receptors, they suggest.

“Our new technique means we can get a real insight into how individual cells are disrupted by heart failure,” commented Dr Julia Gorelik, corresponding author from the National Heart and Lung Institute. “The main question for our future research will be to understand whether drugs can prevent the beta2-AR from moving in the cell and how this might help us to fight heart failure.”