Calcium sparks

A calcium spark is the microscopic release of calcium (Ca²⁺) from a store known as the sarcoplasmic reticulum (SR), located within muscle cells. This release occurs through an ion channel within the membrane of the SR, known as a ryanodine receptor (RyR), which opens upon activation. This process is important as it helps to maintain Ca²⁺ concentration within the cell. It also initiates muscle contraction in skeletal and cardiac muscles and muscle relaxation in smooth muscles. Ca²⁺ sparks are important in physiology as they show how Ca²⁺ can be used at a subcellular level, to signal both local changes, known as local control, as well as whole cell changes.

As mentioned above, Ca²⁺ sparks depend on the opening of ryanodine receptors, of which there are three types:

Opening of the channel allows Ca²⁺ to pass from the SR, into the cell. This increases the local Ca²⁺ concentration around the RyR, by a factor of 10. Calcium sparks can either be evoked or spontaneous, as described below.

Electrical impulses, known as action potentials, travel along the cell membrane (sarcolemma) of muscle cells. Located in the sarcolemma of smooth muscle cells are receptors, called dihydropyridine receptors (DHPR). In skeletal and cardiac muscle cells, however, these receptors are located within structures known as T-tubules, that are extensions of the plasma membrane penetrating deep into the cell (see figure 1). These DHPRs are located directly opposite to the ryanodine receptors, located on the sarcoplasmic reticulum and activation, by the action potential causes the DHPRs to change shape.

In cardiac and smooth muscle, activation of the DHPR results in it forming an ion channel. This allows Ca²⁺ to pass into the cell, increasing the local Ca²⁺ concentration, around the RyR. When four Ca²⁺ molecules bind to the RyR, it opens, resulting in a larger release of Ca²⁺, from the SR . This process, of using Ca²⁺ to activate release of Ca²⁺ from the SR is known as calcium-induced calcium release.

However, in skeletal muscle the DHPR touches the RyR. Therefore, the shape change of the DHPR activates the RyR directly, without the need for Ca²⁺ to flood into the cell first. This causes the RyR to open, allowing Ca²⁺ to be released from the SR.

Ca²⁺ sparks can also occur in cells at rest (i.e. cells that have not been stimulated by an action potential). This occurs roughly 100 times every second in each cell and is a result of Ca²⁺ concentration being too high. An increase in Ca²⁺ within the SR is thought to bind to Ca²⁺ sensitive sites on the inside of the RyR causing the channel to open. As well as this, a protein called calsequestrin (found within the SR) detaches from the RyR, when calcium concentration is too high, again allowing the channel to open (see sarcoplasmic reticulum for more details). Similarly, a decrease in Ca²⁺ concentration within the SR has also proven to lower RyR sensitivity. This is thought to be due to the calsequestrin binding more strongly to the RyR, preventing it from opening and decreasing the likelihood of a spontaneous spark.

There are roughly 10,000 clusters of ryanodine receptors within a single cardiac cell, with each cluster containing around 100 ryanodine receptors. During a single spontaneous spark, when Ca²⁺ is released from the SR, the Ca²⁺ diffuses throughout the cell. As the RyRs in the heart are activated by Ca²⁺, the movement of the Ca²⁺ released during a spontaneous spark, can activate other neighbouring RyRs within the same cluster. However, there usually isn't enough Ca²⁺ present in a single spark to reach a neighbouring cluster of receptors. The calcium can, however, signal back to the DHPR causing it to close and preventing further influx of calcium. This is known as negative feedback.