Researchers at Imperial College London have developed a new cellular physiology imaging technique called Scanning Ion Conductance Microscopy (SICM) to analyze the surface of cardiac muscle cells. The new method, based on a combination between nanoscale live-cell scanning ion conductance and fluorescence resonance energy transfer microscopy, is already answering some questions about the relationship of heart failure and ischemia to myocardial health.
There are two types of receptors for adrenaline. The first, beta1AR, strongly stimulates the heart to contract and it can also induce cell damage in the long term. The second, beta2AR, can slightly stimulate contraction but it also has special protective properties. For today’s study, the researchers combined SICM with new chemical probes which give fluorescent signals when beta1AR or beta2AR is activated.
They found that the beta2AR receptors are normally anchored in the t-tubules, but in those cells damaged by heart failure they change location and move into the same space as beta1AR receptors. The researchers believe that this altered distribution of receptors might affect the beta2AR receptors’ ability to protect cells, and lead to more rapid degeneration of the failing heart.
One of the most important categories of drugs for slowing the development of heart failure are the beta-blockers, which prevent adrenaline from affecting the heart cells by targeting the beta receptors. The new finding increases understanding of what happens to the two receptors in heart failure and could lead to the design of improved beta-blockers. It may eventually help resolve an existing debate about whether it is better to block the beta2AR receptors as well as the beta1AR.
For the study, the researchers looked at single living cardiac muscle cells in a culture dish, taken from healthy or failing rat hearts. They stimulated the beta1AR and beta2AR receptors using drugs applied via nanopipette inside the t-tubules on the heart muscle cell.
Abstract in Science: β2-Adrenergic Receptor Redistribution in Heart Failure Changes cAMP Compartmentation
Press release: Researchers gain detailed insight into failing heart cells using new nano-technique …
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