Channelopathies are diseases that have as their underlying feature mutations or dysregulation of ion channels. Such diseases are frequently associated with excitable cells, including muscle. In the various forms of clinical myotonia, muscle relaxation is prolonged after voluntary contraction. The molecular bases of myotonias are due to dysfunction of channels that shape the action potential. Myotonia dystrophy is caused by an autosomal dominant mutation that leads to overexpression of a K+ channel (although the mutation is not at the K+ channel).
A variety of myotonias are associated with mutations in Na+ channels (eg: hyperkalemic periodic paralysis, paramyotonia congenita, or Na+ channel congenita) or CI– channels (eg: dominant or recessive myotonia congenita}. Myasthenia, defined as abnormal muscle weakness or disease, can also be related to loss of ion channel function in the muscle. In congenital myasthenia, the patient has an inheritable disorder of one of a group of ion channels necessary for the transmission of neuronal signaling to muscle response.
Mutations in Ca2+ channels that allow for neuronal transmitter release or in the acetylcholine receptor nonspecific cation channels, important in recognition of neuronal transmitters, have both been shown to cause congenital myasthenia. Alterations of channel functions can also occur via autoimmune diseases, such as that observed in myasthenia gravis. In this disease, antibodies to the nicotinic acetylcholine receptor can reduce its functional presence at the muscle membrane by up to 80%, and thus limit muscle response to neuronal transmitter release.
Channelopathies can also occur in the Ca2+ release channels in muscle (ryanodine receptors) that amplify the Ca2+ response within the cell. Such mutations can cause malignant hyperthermia. Patients with this condition display normal muscle function under normal conditions. However, certain anesthetic agents, or in rare cases exposure to high environmental heat or strenuous exercise, can trigger an abnormal release of Ca2+ from the sarcoplasmic reticulum in the muscle cell, resulting in sustained muscle contraction and heat production. In severe cases, fatality can occur.