Understanding Heart Failure Mechanisms
Researchers from the University of Bristol, in the United Kingdom, recently managed to resolve the mystery behind the mechanism through which the heart regulates its contractions. Their findings, which could lead to better understanding of heart failures, have been published at the end of this week in the journal Biophysics. The contraction of the heart’s muscles is switched on by the influx of calcium within the muscular cells. When the electrical signal action potential, mediated by very small amounts of calcium, reaches the cell it causes the release of calcium from intracellular storing organelles. Researchers showed interest in this mechanism due to the fact that both the action potential and the response involves the use of calcium, and the amount of calcium that triggers the release of intracellular calcium is very small.
Professor Mark Cannell and his research team from the School of Physiology, within the University of Bristol, found an answer to this problem almost 20 years ago, in the early 90’s. They found out that the release of calcium was time-dependent, which allowed for the calcium releasing events to be graded. The micro-events leading to the release of intracellular calcium from their storing organelles, called sarcoplasmic reticulum, are known as ‘calcium sparks’. In the heart muscle, these sparks occur when clusters of ryanodine receptors are activated by the calcium influx. Even though each micro-event should have a regenerative effect, the time-dependence results in ‘calcium sparks’ not activating due to the fact that the trigger had already passed its location. However, their discovery did not find out why these calcium sparks eventually terminated themselves.
For the current study, a team formed by researchers led by Professor Cannell and Doctor Laver, discovered the answer to the question. The research team created a 3D model of the releasing mechanism and its sensitivity towards calcium. Their computer model revealed what they call ‘induction decay’ a process through which there is an automatic release termination, without the need of other mechanisms. As a result, one of the keys to understanding the cardiac contraction regulation might have been resolved. This discovery could lead to the better understanding of heart failures, due to the fact that precedent studies have shown that in case of a heart failure, the calcium releasing mechanism is involved. “Thanks to sophisticated computer modeling, we have been able provide the necessary insight into the complex behavior of this fundamental system”, concluded Professor Cannell