CACNA1S gene

The CACNA1S gene provides instructions for making calcium channels that are abundant in muscles used for movement (skeletal muscles). For the body to move normally, these muscles must tense (contract) and relax in a coordinated way. Muscle contractions are triggered by the flow of certain ions into muscle cells. Channels made with the CACNA1S protein control the transport of calcium ions into muscle cells and are part of the cellular machinery that initiates muscle contractions.

CACNA1S gene calcium voltage-gated channel subunit alpha1 S

Normal Function
The CACNA1S gene provides instructions for making the main piece (subunit) of a structure called a calcium channel. Channels containing the CACNA1S protein are found in muscles used for movement (skeletal muscles). These skeletal muscle calcium channels play a key role in a process called excitation-contraction coupling, by which electrical signals (excitation) trigger muscle tensing (contraction).
Calcium channels made with the CACNA1S subunit are located in the outer membrane of muscle cells, so they can transmit electrical signals from the cell surface to inside the cell. The channels interact with another type of calcium channel called ryanodine receptor 1 (RYR1) channels (produced from the RYR1 gene). RYR1 channels are located in the membrane of a structure inside the cell that stores calcium ions. Signals transmitted by CACNA1S-containing channels turn on (activate) RYR1 channels, which then release calcium ions inside the cells. The resulting increase in calcium ion concentration within muscle cells stimulates muscles to contract, allowing the body to move.

Health Conditions Related to Genetic Changes
Hypokalemic periodic paralysis At least 11 mutations in the CACNA1S gene have been identified in people with hypokalemic periodic paralysis, a condition that causes episodes of extreme muscle weakness, usually in the arms and legs. CACNA1S gene mutations cause up to 70 percent of all cases of this disorder.
Mutations in the CACNA1S gene change single protein building blocks (amino acids) used to make the CACNA1S protein, which alters the structure and function of calcium channels in skeletal muscle cells. The altered channels open more slowly than usual, reducing the flow of calcium ions into these cells. This disruption in calcium ion transport prevents muscles from contracting normally. It is unclear precisely how these changes lead to episodes of muscle weakness in people with hypokalemic periodic paralysis.

Malignant hyperthermia
CACNA1S gene mutations account for a very small percentage of all cases of malignant hyperthermia. Malignant hyperthermia is a severe reaction to particular anesthetic drugs that are often used during surgery and other invasive procedures. The reaction involves a high fever (hyperthermia), a rapid heart rate, muscle rigidity, breakdown of muscle fibers (rhabdomyolysis), and increased acid levels in the blood and other tissues (acidosis). Complications can be life-threatening without prompt treatment. Researchers have identified several mutations in the CACNA1S gene that are associated with an increased risk of this condition. These mutations replace single amino acids in the CACNA1S protein.
Channels made with the altered CACNA1S proteins likely activate the RYR1 channel improperly in response to certain drugs (particularly some anesthetics and a type of muscle relaxant used during surgery). As a result, large amounts of calcium ions are released from storage within muscle cells. An overabundance of calcium ions activates processes that generate heat (leading to increased body temperature) and produce excess acid (leading to acidosis). An increase in calcium ion concentration also causes skeletal muscles to contract abnormally, which leads to muscle rigidity.

Chromosomal Location
Cytogenetic Location: 1q32.1, which is the long (q) arm of chromosome 1 at position 32.