A research team from the University of Pittsburgh School of Medicine and Carnegie Mellon University claim to have developed unique chemical dyes that make it possible to see action potentials , or voltage changes, of cardiac cells including those deep inside the heart, which trigger and determine the pace of heartbeats. This they stated was something that the naked eye has never seen before, and to be able to see the precise events from regular rhythm to irregular heartbeats would help researchers to understand better the causes of arrhythmias and sudden cardiac death.
Describing seven of the "Pittsburgh" dyes, PGH I to IV and VI to VIII, for short, in the current issue of the Journal of Membrane Biology, they explain that the PGH dyes are able to follow the electrical activity of cells several layers below the surface of the heart where the cardiac contractions are initiated and propagated.
They hope that this would help to answer the important question of what exactly causes arrhythmias and sudden cardiac death. Explaining that these dyes have so far proved to be particularly important in recording, membrane potential changes and capturing in detail, the actual, the synchronicity or asynchronicity of the heart. Lead author Guy Salama, Ph.D., professor of cell biology and physiology at the University of Pittsburgh School of Medicine said that obtaining images like these had long been a challenge due to confounding motions of the heart.
Dr. Salama teamed up with Alan Waggoner, Ph.D., and Lauren Ernst, Ph.D., of Carnegie Mellon's Molecular Biosensor and Imaging Centre (MBIC) to developed the long wavelength, voltage-sensitive dyes, which would be capable of yielding images of a cell as its voltage changes. They explained that the PGH dyes emit fluorescent light according to changes in voltage across cell membranes that are produced by activity of sodium and potassium channels, which open and close as the cell's voltage changes. The dyes make it possible to actually see changes in the electrical potential of a single cell, multiple cells, or even the entire heart, they said.
Importantly, the researchers also found that the PGH dyes could also be made of use simultaneously with other probes, such as for calcium, to provide a more complete picture of the processes influencing normal and abnormal rhythms. They found that, they could now map, in real time, action potentials, or voltage changes, of cardiac cells below the surface of the heart while following calcium transients (a measure of the local force generated by each cell) during each action potential.
Dr. Waggoner, professor of biological sciences and MBIC director, Mellon College of Science, Carnegie Mellon University, said that, a unique feature of the PGH dyes is their large Stokes shifts, the wavelength difference between excitation and fluorescence, which make them particularly advantageous for simultaneously mapping action potentials and calcium transients with less interference and therefore greater sensitivity.
Explaining that longer wavelengths of light can penetrate farther into tissue, Dr. Ernst, senior research scientist at Carnegie Mellon's MBIC, noted that one of the dyes in particular exhibited excitation at wavelengths far into the red region of the spectrum, significantly longer than the other dyes. And this dye can image the electrical activity of cells deeper inside the heart, he stated.
The researchers are trying to understand the mechanisms which influences the long QT intervals, the time that it takes a depolarised cell to return to its repolarized state on animal models. They explain that it is widely accepted that structural abnormalities of potassium channels are often associated with a hereditary condition called Long QT Syndrome, which affects between 5,000 and 10,000 people in the United States and can have fatal consequences. But that it is normal for women of pre-menopausal age to have slightly prolonged QT intervals, though the reasons for it is not yet understood.
They also state that the current view is that abnormal potassium channels cause long QT intervals, and that this could be what causes arrhythmias as well. But the researchers state that not everyone with a long QT interval experiences arrhythmias. They say that many common used drugs, including the antibiotic erythromycin, decongestants that containing epinephrine and anti-depressants, can block potassium channels, any woman in her 30s and 40s can be at risk for drug-induced ventricular arrhythmias, and potentially, sudden cardiac death
Dr. Salama explains that they're beginning to see that the determining factor is an added problem involving the sodium-calcium exchanger and may help explain the differences in risk between men and women. She said that the new voltage-sensitive dyes, together with novel optical techniques, have greatly enhanced the understanding of how the heart works. The researchers hope to continue their work towards the development of a high-speed, depth-resolved 3-D imaging system that makes use of what may be the fastest camera at 100x100 pixels, with the ability to capture 10,000 images per second.
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