Frank-Starling relationship

More than a century ago, two physiologists, Otto Frank and Ernest Starling discovered that as the heart gets filled up with more blood during diastole, it contracts harder and pumps out more blood during systole. So they came up with the Frank Starling Law to explain this relationship.

To understand this relationship, let’s zoom into the wall of the ventricles. The bulk of these walls is made up of short, branched cardiac muscle cells packed one next to the other. Zooming in further, if we look inside the muscle cells, we see bundles of myofibrils, or long chains of sarcomeres. The sarcomere is the smallest structure in the muscle that is capable of contracting so it's considered the basic contractile unit of the muscle. The sarcomere has two Z discs that form its boundary and a M line in the middle. Attached to the Z disc are thin filaments made of actin protein. These actin filaments have structural polarity which means both ends of the filament look different. We can think of it like an arrow with the pointed end being the “minus end,” pointing towards the M line, and the tail end being the “plus end,” attached to the Z disc. Just like an arrow, the actin filament can only move in one direction: the direction it’s pointed at. Attached to the M line are the myosin filaments which are thick bundles of myosin proteins with two globular heads. During a muscle contraction, the myosin heads grabs onto the actin filaments, and pull them towards the M line which brings the two Z discs closer together.

Overall, the amount of tension developed, or the force of muscle contraction during systole, depends on the number of myosin heads that bind to actin. And this number directly depends on the length of the overlapping section between actin and myosin filaments. The length of the overlapping section depends on the overall length of the sarcomere. And the length of the sarcomere depends on how much blood fills the ventricle during diastole - because that affects how stretched out the overall muscle wall and each sarcomere within it end up being. This relationship is known as the cardiac length-tension relationship and it can be shown by this graph, with the sarcomere length or the ventricular end- diastolic volume on the x axis and the tension or pressure developed within the ventricle, during their contraction, or systole, on the y axis.

So let’s imagine that the ventricles are mostly empty, with almost no blood in them. This would mean that there’s nothing stretching the muscles in the ventricular wall, so the length of sarcomeres are really short. At this length, the two Z discs are pulled close to each and there’s not much room for further contraction. Furthermore, the actin filaments from each side of the sarcomere crosses the M line and overlap. Since actin can be pulled only in one direction- towards the midline, myosin has to attach and pull the actin filament with the right structural polarity: the one pointing in the same direction as that the myosin pulls. So, when the actin filaments overlap, myosin is prevented from binding to its own actin filament by the actin filament from the other side with the wrong polarity. As a result, very few myosin- actin attachments are made and the cells can contract only very weakly during systole. On the graph, we can see near the point of origin, the short length of myocardial fibers corresponds with a low contractile force.

As the ventricles fill with more blood returning through the veins, their walls get more and more stretched and that stretches out every single sarcomere in the muscle cells as well. This means that there’s more space, and no actin overlapping which allows more myosin heads to properly interact with actin and as a result, create more force, or tension, during contraction. Looking at the graph, this would make our curve move steadily upwards with increasing force as there’s increasing volume. This stretching can go on until it exceeds a maximal point, after which things start getting too stretched out. This means the Z discs are so far apart from each other that there’s only little overlap between actin and myosin filaments and actin gets out of reach from myosin. As a result, there's a decreased number of myosin heads that manage to attach to actin and pull it towards the M line. This leads to a decreased force of contraction, so the curve starts falling off again.