Genomes and Genes
Gene Symbol: Cacna1s
Description: calcium voltage-gated channel subunit alpha1 S
Alias: Cchl1a3, RGD1565743, voltage-dependent L-type calcium channel subunit alpha-1S, ROB1, calcium channel, L type, alpha-1 polypeptide, isoform 3, skeletal muscle, calcium channel, voltage-dependent, L type, alpha 1S subunit, voltage-gated calcium channel subunit alpha Cav1.1
- Obermair G, Kugler G, Baumgartner S, Tuluc P, Grabner M, Flucher B. The Ca2+ channel alpha2delta-1 subunit determines Ca2+ current kinetics in skeletal muscle but not targeting of alpha1S or excitation-contraction coupling. J Biol Chem. 2005;280:2229-37 pubmed..However, this subunit is not essential for targeting of Ca(2+) channels or for their primary physiological role in activating skeletal muscle excitation-contraction coupling. ..
- Catterall W. Voltage-gated calcium channels. Cold Spring Harb Perspect Biol. 2011;3:a003947 pubmed publisher..This article presents the molecular relationships and physiological functions of these Ca(2+) channel proteins and provides information on their molecular, genetic, physiological, and pharmacological properties. ..
- Wang M, Hao L, Guo F, Zhong B, Zhong X, Yuan J, et al. Decreased intracellular [Ca2+ ] coincides with reduced expression of Dhpr?1s, RyR1, and diaphragmatic dysfunction in a rat model of sepsis. Muscle Nerve. 2017;56:1128-1136 pubmed publisher..Decreased intracellular [Ca2+ ] coincides with diaphragmatic contractility and decreased expression of DHPR?1s and RyR1 in sepsis. Muscle Nerve 56: 1128-1136, 2017. ..
- Powell J, Fambrough D. Electrical properties of normal and dysgenic mouse skeletal muscle in culture. J Cell Physiol. 1973;82:21-38 pubmed
- Gregg R, Messing A, Strube C, Beurg M, Moss R, Behan M, et al. Absence of the beta subunit (cchb1) of the skeletal muscle dihydropyridine receptor alters expression of the alpha 1 subunit and eliminates excitation-contraction coupling. Proc Natl Acad Sci U S A. 1996;93:13961-6 pubmed
- Pai A. DEVELOPMENTAL GENETICS OF A LETHAL MUTATION, MUSCULAR DYSGENESIS (MDG), IN THE MOUSE. I. GENETIC ANALYSIS AND GROSS MORPHOLOGY. Dev Biol. 1965;11:82-92 pubmed
- Elbaz A, Vale Santos J, Jurkat Rott K, Lapie P, Ophoff R, Bady B, et al. Hypokalemic periodic paralysis and the dihydropyridine receptor (CACNL1A3): genotype/phenotype correlations for two predominant mutations and evidence for the absence of a founder effect in 16 caucasian families. Am J Hum Genet. 1995;56:374-80 pubmed
- Monnier N, Procaccio V, Stieglitz P, Lunardi J. Malignant-hyperthermia susceptibility is associated with a mutation of the alpha 1-subunit of the human dihydropyridine-sensitive L-type voltage-dependent calcium-channel receptor in skeletal muscle. Am J Hum Genet. 1997;60:1316-25 pubmed..This report is the first direct evidence that the skeletal muscle VDCC is involved in MHS, and it suggests a direct interaction between the skeletal muscle VDCC and the ryanodine receptor in the skeletal muscle sarcoplasmic reticulum. ..
- Flucher B, Conti A, Takeshima H, Sorrentino V. Type 3 and type 1 ryanodine receptors are localized in triads of the same mammalian skeletal muscle fibers. J Cell Biol. 1999;146:621-30 pubmed..The localization of RyR3 in skeletal muscle triads, together with RyR1, is consistent with an accessory function of RyR3 in skeletal muscle excitation-contraction coupling. ..
- Powell J, Rieger F, Blondet B, Dreyfus P, Pincon Raymond M. Distribution and quantification of ACh receptors and innervation in diaphragm muscle of normal and mdg mouse embryos. Dev Biol. 1984;101:168-80 pubmed..Possible causes of the excessive nerve branching in the mutant are discussed in light of generalized nerve sprouting found in paralyzed muscle. ..
- Herasse M, Parain K, Marty I, Monnier N, Kaindl A, Leroy J, et al. Abnormal distribution of calcium-handling proteins: a novel distinctive marker in core myopathies. J Neuropathol Exp Neurol. 2007;66:57-65 pubmed
- Kraner S, Wang Q, Novak K, Cheng D, Cool D, Peng J, et al. Upregulation of the CaV 1.1-ryanodine receptor complex in a rat model of critical illness myopathy. Am J Physiol Regul Integr Comp Physiol. 2011;300:R1384-91 pubmed publisher..There was also selective degradation of myosin heavy chain relative to actin in CIM muscle. Taken together, our findings suggest that increased Ca(2+) release from the sarcoplasmic reticulum may contribute to pathology in CIM. ..
- Beam K, Knudson C, Powell J. A lethal mutation in mice eliminates the slow calcium current in skeletal muscle cells. Nature. 1986;320:168-70 pubmed..The effects of the mutation raise important questions about the relationship between the slow calcium current and skeletal muscle E-C coupling. ..
- Tanaka H, Furuya T, Kameda N, Kobayashi T, Mizusawa H. Triad proteins and intracellular Ca2+ transients during development of human skeletal muscle cells in aneural and innervated cultures. J Muscle Res Cell Motil. 2000;21:507-26 pubmed
- Joffroy S, Letellier T, Rossignol R, Malgat M, Delage J, Powell J, et al. Modification of mitochondrial metabolism in fibroblasts from mice with a skeletal muscle mutation (muscular dysgenesis). Evidence of embryonic communication between myoblasts and fibroblasts. Differentiation. 2000;65:261-70 pubmed..Synergistic activities of this type should be considered when studying the course of pathologies in different types of muscle diseases. ..
- Yu A, Hebert S, Brenner B, Lytton J. Molecular characterization and nephron distribution of a family of transcripts encoding the pore-forming subunit of Ca2+ channels in the kidney. Proc Natl Acad Sci U S A. 1992;89:10494-8 pubmed..One gene, CaCh4, is expressed primarily in the cortex, and by microdissected-tubule PCR was found predominantly in the distal convoluted tubule, consistent with a role in transepithelial Ca2+ reabsorption at this site. ..
- Chaudhari N. A single nucleotide deletion in the skeletal muscle-specific calcium channel transcript of muscular dysgenesis (mdg) mice. J Biol Chem. 1992;267:25636-9 pubmed..It is possible that premature termination of translation renders the mutant mRNA subject to degradation by nucleases. This work resolves a long-standing controversy on the nature of the primary genetic defect in muscular dysgenesis. ..
- Rieger F, Cross D, Peterson A, Pincon Raymond M, Tretjakoff I. Disease expression in +-/+- ----mdg/mdg mouse chimeras: evidence for an extramuscular component in the pathogenesis of both dysgenic abnormal diaphragm innervation and skeletal muscle 16 S acetylcholinesterase deficiency. Dev Biol. 1984;106:296-306 pubmed
- Ashby P, Pincon Raymond M, Harris A. Regulation of myogenesis in paralyzed muscles in the mouse mutants peroneal muscular atrophy and muscular dysgenesis. Dev Biol. 1993;156:529-36 pubmed
- Seigneurin Venin S, Song M, Pincon Raymond M, Rieger F, Garcia L. Restoration of normal ultrastructure after expression of the alpha 1 subunit of the L-type Ca2+ channel in dysgenic myotubes. FEBS Lett. 1994;342:129-34 pubmed
- Conklin M, Powers P, Gregg R, Coronado R. Ca2+ sparks in embryonic mouse skeletal muscle selectively deficient in dihydropyridine receptor alpha1S or beta1a subunits. Biophys J. 1999;76:657-69 pubmed..However, excitation-contraction coupling is not essential for Ca2+ spark formation in these cells. ..
- Tanabe T, Takeshima H, Mikami A, Flockerzi V, Takahashi H, Kangawa K, et al. Primary structure of the receptor for calcium channel blockers from skeletal muscle. Nature. 1987;328:313-8 pubmed
- Shtifman A, Paolini C, Lopez J, Allen P, Protasi F. Ca2+ influx through alpha1S DHPR may play a role in regulating Ca2+ release from RyR1 in skeletal muscle. Am J Physiol Cell Physiol. 2004;286:C73-8 pubmed
- Rieger F, Pincon Raymond M. Muscle and nerve in muscular dysgenesis in the mouse at birth: sprouting and multiple innervation. Dev Biol. 1981;87:85-101 pubmed
- Houinato D, Laleye A, Adjien C, Adjagba M, Sternberg D, Hilbert P, et al. Hypokalaemic periodic paralysis due to the CACNA1S R1239H mutation in a large African family. Neuromuscul Disord. 2007;17:419-22 pubmedHypokalaemic periodic paralysis (HypoKPP) is a skeletal muscle channelopathy caused by mutations in calcium (CACNA1S) and sodium (SCN4A) channel subunits...
- Chin H, Krall M, Kim H, Kozak C, Mock B. The gene for the alpha 1 subunit of the skeletal muscle dihydropyridine-sensitive calcium channel (Cchl1a3) maps to mouse chromosome 1. Genomics. 1992;14:1089-91 pubmedb>Cchl1a3 encodes the dihydropyridine-sensitive calcium channel alpha 1 subunit isoform predominantly expressed in skeletal muscle. mdg (muscular dysgenesis) has previously been implicated as a mutant allele of this gene...
- Tanaka N, Ishii H, Yin C, Koyama M, Sakuma Y, Kato M. Voltage-gated Ca2+ channel mRNAs and T-type Ca2+ currents in rat gonadotropin-releasing hormone neurons. J Physiol Sci. 2010;60:195-204 pubmed publisher..6 s. These results indicate that rat GnRH neurons express subtypes of the alpha(1) subunit for all five types of voltage-gated Ca(2+) channel, and that alpha(1H) was the dominant subtype in T-type Ca(2+) channels. ..
- Joffroy S, Dourdin N, Delage J, Cottin P, Koenig J, Brustis J. M-calpain levels increase during fusion of myoblasts in the mutant muscular dysgenesis (mdg) mouse. Int J Dev Biol. 2000;44:421-8 pubmed..Taking into account these observations, it is clear from our data that the muscular dysgenesis mouse provides a relevant model to study myoblast fusion and that m-calpain is involved in this process. ..
- Jiao G, Hao L, Gao C, Chen L, Sun X, Yang H, et al. Reduced DHPR?1S and RyR1 expression levels are associated with diaphragm contractile dysfunction during sepsis. Muscle Nerve. 2013;48:745-51 pubmed publisher..Weakened diaphragm contraction in the septic rats was associated with reduced mRNA and protein expression of DHPR?1s and RyR1, the isoforms of skeletal muscles. ..
- Peterson A, Pena S. Relationship of genotype and in vitro contractility in mdg/mdg in equilibrium +/+ "mosaic" myotubes. Muscle Nerve. 1984;7:194-203 pubmed..Only a very small proportion of genotypically normal myonuclei were required for expression of an apparently normal contractile phenotype. ..
- Atchley W, Herring S, Riska B, Plummer A. Effects of the muscular dysgenesis gene on developmental stability in the mouse mandible. J Craniofac Genet Dev Biol. 1984;4:179-89 pubmed..Traits not showing significantly increased instability in +/mdg mice bear no clear relationship to either muscle attachment areas or to the mdg/mdg phenotype. ..
- Barry E, Gesek F, Froehner S, Friedman P. Multiple calcium channel transcripts in rat osteosarcoma cells: selective activation of alpha 1D isoform by parathyroid hormone. Proc Natl Acad Sci U S A. 1995;92:10914-8 pubmed..The present results provide evidence for the expression of three distinct calcium channel alpha 1-subunit isoforms in an osteoblast-like cell line. We conclude that the alpha 1D isoform is selectively activated by parathyroid hormone. ..
- Morrill J, Brown R, Cannon S. Gating of the L-type Ca channel in human skeletal myotubes: an activation defect caused by the hypokalemic periodic paralysis mutation R528H. J Neurosci. 1998;18:10320-34 pubmed..The R528H mutation had no effect on the kinetics or voltage dependence of inactivation...
- Ohrtman J, Ritter B, Polster A, Beam K, Papadopoulos S. Sequence differences in the IQ motifs of CaV1.1 and CaV1.2 strongly impact calmodulin binding and calcium-dependent inactivation. J Biol Chem. 2008;283:29301-11 pubmed publisher..Thus, our results reveal that a conserved difference between the IQ motifs of Ca(V)1.2 and Ca(V)1.1 has a profound effect on both CaM binding and calcium-dependent inactivation. ..