A long-withstanding puzzle as to how the heart regulates its beat appears to have been solved, paving way for better understanding of heart failure.
When the heart beats (contracts), the contractile machinery is switched on by an increase in calcium within the cell, according to researchers.
This increase is produced by a release from intracellular stores activated by a small influx of calcium into the cell during the cardiac electrical signal - known as the action potential, they said.
This apparently simple process raised an important question, since the trigger signal was smaller than the release and both involve calcium how could the system be graded - since once the release is started it should overcome the trigger signal and be fully regenerative.
Researchers led by Professor Mark Cannell from the University of Bristol's School of Physiology and Pharmacology with Dr Laver from Hunter Medical Research Institute in Australia constructed a 3-dimensional computer model of the release machinery incorporating measurements of the calcium sensitivity of the release mechanism.
They found that the key to this puzzle is in the calcium dependence of the closed time of the channels that release calcium and the microscopic domain in which they reside.
This model showed automatic release termination without having to invoke any other mechanism a process they called "induction decay".
Therefore, a key piece of the puzzle as how the heart regulates contraction appears to have been solved, and this paves the way to improved understanding of what goes wrong when the heart fails - because there is good evidence that the calcium release mechanism becomes faulty in heart failure.
"These intracellular processes only occur on the molecular scale which is difficult, if not impossible, to image and study within living cells. Thanks to sophisticated computer modelling, we have been able provide the necessary insight into the complex behaviour of this fundamental system," Cannell said.
The study was published in the journal Biophysics.