- Peptide CGNVDPDESARIS, corresponding to amino acid residues 506-518 of rat CaV1.1 (Accession Q02485). 2nd extracellular loop, domain IV.
- Rat skeletal muscle membranes (1:200-1:1000).
- Western blot analysis of rat skeletal muscle:1. Anti-CaV1.1 (CACNA1S) (extracellular) Antibody (#ACC-314), (1:200).
2. Anti-CaV1.1 (CACNA1S) (extracellular) Antibody, preincubated with Cav1.1/CACNA1S (extracellular) Blocking Peptide (#BLP-CC314).
- Rat muscle sections (1:100).
Voltage-gated Ca2+ channels (VGCCs) serve as key transducers coupling changes in cell surface membrane potential with local intracellular Ca2+ pathways. Among the three families of VGCCs, L-type Ca2+ channels (L-VGCCs), include four different isoforms of the α1 pore-forming subunit: CaV1.1, CaV1.2, CaV1.3 and CaV1.41.
CaV1.1 (α1S) is the prototypical VGCCs. It was the first member of the CaV family to be cloned2. CaV1.1 is a single polypeptide composed of four relatively conserved repeats (I, II, II and IV) containing six α-helices a piece. The fourth α-helix of each repeat has a regularly spaced sequence of basic residues that is believed to be critical for voltage-sensing. The I–II-linker is the site of interaction with the intracellular β1a subunit3.
CaV1.1 is expressed solely in skeletal muscle. It is localized in regions of the T-tubular membrane that are closely opposed to the sarcoplasmic reticulum (the TSR junction). The primary role of CaV1.1 is to serve as the voltage sensor for skeletal muscle-type excitation contraction (EC) coupling4.
Mutations in CaV1.1 have been identified as causative for two congenital muscle pathophysiologies: hypokalemic periodic paralysis5 (HypoKPP) and malignant hyperthermia6.