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. Activation As mentioned above, Ca2+ sparks depend on the opening of ryanodine receptors, of which there are three types: Type 1 – found mainly in skeletal muscle Type 2 – found mainly in the heart Type 3 – found mainly in the brain 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. Evoked 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. Spontaneous Ca2+ sparks can