Voltage-dependent L-type calcium channel subunit alpha-1S (Cav1.1) (Cav1.1)

The Voltage-dependent L-type calcium channel subunit alpha-1S (Cav1.1) is the pore-forming and voltage-sensing component of the L-type calcium channel complex found predominantly in the skeletal muscle sarcolemma and transverse tubules [1.1.1, 1.2.1]. It plays a fundamental role in excitation-contraction coupling by acting as a voltage sensor that mechanically activates the ryanodine receptor 1 (RyR1) in the sarcoplasmic reticulum, thereby triggering the release of intracellular calcium required for muscle contraction [1.3.1, 1.4.3]. Mutations in the CACNA1S gene are associated with several neuromuscular disorders, including hypokalemic periodic paralysis, where patients experience episodes of extreme muscle weakness, and malignant hyperthermia susceptibility, a life-threatening hypermetabolic reaction to volatile anesthetics [1.2.1, 1.3.2]. In malignant hyperthermia, specific variants in Cav1.1 cause an abnormal interaction with RyR1, leading to uncontrolled calcium release and muscle rigidity when exposed to triggers like halothane or succinylcholine [1.4.3, 1.4.4]. While Cav1.1 is the classic "dihydropyridine receptor" and binds drugs like nifedipine with high affinity, most clinical L-type calcium channel blockers are used to target the Cav1.2 isoform in the cardiovascular system [1.4.2, 1.4.5]. Beyond its role in muscle physiology, recent research has suggested that Cav1.1 may also serve as a cellular entry factor for certain arenaviruses, highlighting its potential as a broader therapeutic target [1.4.1]. Diagnostic genetic testing for CACNA1S mutations is a critical biomarker for identifying individuals at risk for anesthetic complications or periodic paralysis [1.4.2, 1.4.4].

Other names

CACNA1SDHPRDihydropyridine receptorCalcium channel, L type, alpha-1 polypeptide, skeletal muscleCACNL1A3CCHL1A3HOKPP1MHS5

Voltage-gated calcium channel blockade and modulation of mechanical coupling with ryanodine receptors to regulate intracellular calcium release.