Nano-imaging technique gives clues to failing hearts
2 March 2010
The research, part funded by the Wellcome Trust, used a technique known as nanoscale scanning ion conductance microscopy - SICM - to look at the surface of single living heart muscle cells from healthy or failing rat hearts grown in culture.
Dr Julia Gorelik from the National Heart and Lung Institute at Imperial College London, who led the research, said: "Our new technique means we can get a real insight into how individual cells are disrupted by heart failure. Using nanoscale live-cell microscopy we can scan the surface of heart muscle cells to much greater accuracy than has been possible before and to see tiny structures that affect how the cells function."
Heart failure is a progressive and serious condition in which the heart is unable to supply adequate blood flow to meet the body's needs. Hormones such as adrenaline, which are produced by the body in an attempt to stimulate the weakened heart, can eventually produce further damage and deterioration.
The new study, published online this week in the journal 'Science', reveals that the extra damage caused by adrenaline following heart failure could be the result of changes in the distribution of receptors that help heart cells to respond to adrenaline.
There are two types of adrenaline receptors which have different consequences on heart function. The first, beta1AR, strongly stimulates the heart to contract and can also induce cell damage in the long term. The second, beta2AR, weakly stimulates contraction and has special properties that help protect the heart from damage.
By combining SICM with chemical probes that give fluorescent signals when beta1AR or beta2AR is activated, the team were able to visualise the exact location of the two receptor types on the surface of individual heart muscle cells.
They found that normally, the beta2AR receptors are buried within minute tubes on the surface of the heart muscle cells, known as t-tubules, which carry electrical signals deep into the core of the cell. But in cells that have been damaged by heart failure, these receptors had moved to be in the same location as the beta1AR receptors, in the spaces between t-tubules. The researchers believe that this altered distribution could affect beta2AR receptors' ability to protect cells, leading to more rapid degeneration of the heart.
"Through understanding what's happening on this tiny scale, we can ultimately build up a really detailed picture of what's happening to the heart during heart failure and long term, this should help us to tackle the disease. 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," added Dr Gorelik.
One of the most important categories of drugs for slowing the development of heart failure are the beta-blockers, which prevent adrenaline from damaging heart cells further by targeting the beta receptors. It's hoped that better understanding of what happens to the two types of receptor in heart failure could lead to the design of improved beta-blockers. And the findings could also help to resolve an existing debate about whether it is better to block both types of receptor, or to focus on the damage causing beta1R receptors.
Image: High resolution scanning ion conductance microscopy image of living, healthy heart muscle cell. Credit: Science/AAAS.
Reference
Nikolaev VO et al. Beta2-adrenergic receptor redistribution in heart failure changes cAMP comparmentation. Science 2010 [Epub ahead of print].
