Media Release: Unlocking the secrets of shrews supercharged hearts
Studying the cardiac proteins of ultra-high heart rate mammals leads to an abundance of hope for new therapies for humans with certain types of heart disease
The maximal heart rate of a human is about 200 beats per minute, or 3.3 beats per second. Now compare that to tiny shrews, whose hearts clock an astounding 1000 beats per minute or 17 beats per second during rest. The discovery of an altered heart protein in shrews by researchers at the University of Manitoba and Aarhus University helps explain this difference and could unlock treatment possibilities for people living with certain types of heart disease. The findings are featured in the latest issue of the journal, Science.
Mammal hearts have a protein called “cardiac troponin I” that is involved in the binding of calcium ions during heart contraction. This protein contains two serine amino acids that become temporarily modified during “flight or fight” scenarios when adrenaline is surging.
“This biochemical modification causes muscle fibres of our heart to release calcium ions more quickly after contraction and causes it to relax faster, thus providing the heart with more time to refill with blood during exercise,” says Professor of Environmental and Evolutionary Physiology, University of Manitoba, Kevin Campbell.
By contrast, the DNA region encoding the two serines became inactivated in shrews and moles.
“This means the protein always functions as if it were activated by adrenaline, even when the animal is at rest,” says study lead author William Joyce, then working at Aarhus University, Denmark. “This evolutionary loss permanently removes the brakes on their heart relaxation time, allowing shrews to achieve their extreme heart rates”.
Analysis of this heart protein in bats, which can also exhibit heart rates that exceed 1000 beats per minute, provide a roadmap to how this ability evolved.
“Our examination of bat troponin I indicated that some species can ‘skip over’ the gene region encoding the serine residues when building the protein,” says Campbell. Thus, ancient shrews and moles, like some bats today, were able to make versions of the protein that either lack or contain the serine amino acids. “Evolution then favoured the permanent skipping and subsequent loss of this serine containing exon in shrews and moles, thereby allowing them to evolve even higher heart rates.”
In humans with certain types of heart disease, the protein does not respond normally to adrenaline and researchers are hoping to use this discovery to develop new approaches to tackling this chronic condition.
“Intriguingly, the human troponin I gene has traits that may make it amenable to induction of this same type of exon skipping,” says Joyce.
Once achieved, this intervention would help improve cardiac function in patients with heart failure.
While additional research is required, Joyce says, “It appears nature has realized the solution to improving heart function in the absence of nervous system stimulation can be applied to modern biomedicine.”
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