Excitation-contraction coupling The arrhythmias that those with<unk>  experience are caused by abnormalities in the way that cardiac muscle cells control their levels of calcium. Calcium interacts with the protein fibres or myofibrils inside the cell that allow the cell to contract, and the concentration of calcium within each cell needs to be tightly regulated. During each heartbeat, the concentration of calcium must rise to allow the muscle to contract and then fall to allow the muscle to relax, a process achieved by using a store within the cell known as the sarcoplasmic reticulum. Proteins involved in cardiac calcium cycling At the start of each heartbeat, calcium is released from the sarcoplasmic reticulum through specialised channels known as ryanodine receptors. Ryanodine receptors open when the concentration of calcium near the channel increases. This happens when, in response to an electrical signal from the cell membrane called an action potential, a small amount of calcium flows across the cell membrane into the cell through L-type calcium channels, many of which are located on specialised inpouchings of the membrane called T-tubules designed to bring these surface ion channels close to the sarcoplasmic reticulum. The increase in calcium concentration triggers ryanodine receptors on the sarcoplasmic reticulum to release a puff of calcium known as a calcium spark. Each spark triggers the release of further sparks from neighbouring ryanodine receptors to create an organised rise of calcium throughout the cell known as a calcium transient. At the end of each heartbeat, calcium is pumped back by a protein called SERCA along with its regulatory protein phospholamban. The calcium is then held within the sarcoplasmic reticulum by a protein called calsequestrin. Fine-tuning of this process can be achieved by phosphorylating these proteins. As an example, during exercise catecholamines activate beta-adrenoceptors on the cell surface, which trigger protein kinase A to phosphorylate the L-type calcium channel, increasing the flow of calcium into the cell. Simultaneously, phosphorylation of the regulatory protein phospholamban causes more calcium to be drawn up into the sarcoplasmic reticulum. The overall effect of this is to generate a larger calcium transient with each beat, leading to a more forceful contraction. Calcium-dependent arrhythmias Alterations to the proteins involved in excitation-contraction coupling can disrupt this carefully regulated process. In those with<unk> , the normally tight regulation of calcium can become deranged, leading to arrhythmias. While calcium is generally released from the sarcoplasmic reticulum in response to an action potential, calcium sparks can also occur spontaneously. In a healthy heart, a spontaneous calcium spark is generally an isolated event and goes no further, but if ryanodine receptors or the proteins that regulate them are abnormal, these sparks can trigger releases from neighbouring ryanodine receptors which spread throughout the cell as a calcium wave. These calcium waves are much more likely to occur when cardiac muscle cells are stimulated by catecholamines such as adrenaline, which increase the concentration of calcium within the sarcoplasmic reticulum and sensitise the ryanodine receptors. The uncontrolled wave of calcium can be forced out through the cell membrane via the sodium-calcium exchanger, causing an electric current known as a delayed afterdepolarisation. Afterdepolarisations, if large enough, can trigger additional action potentials, premature<unk>  contractions, or sustained arrhythmias.
Catecholaminergic polymorphic ventricular tachycardia
Benign early repolarization
Junctional ectopic tachycardia
Brugada syndrome
Pre-excitation syndrome
Long QT syndrome
Wandering atrial pacemaker
Andersen–Tawil syndrome