Cav1.2

Calcium channel, voltage-dependent, L type, alpha 1C subunit
250px PDB rendering based on 2be6.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1T0J, 2BE6, 2F3Y, 2F3Z, 2LQC, 3G43, 3OXQ
Identifiers
Symbols	CACNA1C ; CACH2; CACN2; CACNL1A1; CCHL1A1; CaV1.2; LQT8; TS
External IDs	OMIM: 114205 MGI: 103013 HomoloGene: 55484 IUPHAR: 529 ChEMBL: 1940 GeneCards: CACNA1C Gene
Gene ontology Molecular function • voltage-gated calcium channel activity • protein binding • calmodulin binding • high voltage-gated calcium channel activity • protein domain specific binding • metal ion binding • alpha-actinin binding • protein phosphatase 2A binding Cellular component • caveolar macromolecular signaling complex • cytoplasm • cytosol • plasma membrane • voltage-gated calcium channel complex • postsynaptic density • integral component of membrane • Z disc • T-tubule • neuronal cell body • dendritic shaft Biological process • energy reserve metabolic process • positive regulation of cytosolic calcium ion concentration • synaptic transmission • axon guidance • adult walking behavior • regulation of blood pressure • visual learning • regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion • calcium ion-dependent exocytosis • regulation of vasoconstriction • insulin secretion • growth hormone secretion • ion transmembrane transport • regulation of ion transmembrane transport • calcium-mediated signaling using extracellular calcium source • glucose homeostasis • small molecule metabolic process • regulation of organ growth • regulation of insulin secretion • smooth muscle contraction involved in micturition • calcium ion transport into cytosol • calcium ion import • calcium ion transmembrane transport • membrane depolarization during action potential • cell communication by electrical coupling involved in cardiac conduction Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	775	12288
Ensembl	ENSG00000151067	ENSMUSG00000051331
UniProt	Q13936	Q01815
RefSeq (mRNA)	NM_000719	NM_001159533
RefSeq (protein)	NP_000710	NP_001153005
Location (UCSC)	Chr 12: 1.97 – 2.7 Mb	Chr 6: 118.59 – 119.2 Mb
PubMed search	[1]	[2]

Calcium channel, voltage-dependent, L type, alpha 1C subunit (also known as Ca_v1.2) is a protein that in humans is encoded by the CACNA1C gene. Ca_v1.2 is a subunit of L-type voltage-dependent calcium channel.

Structure and function

This gene encodes an alpha-1 subunit of a voltage-dependent calcium channel. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization. The alpha-1 subunit consists of 24 transmembrane segments and forms the pore through which ions pass into the cell. The calcium channel consists of a complex of alpha-1, alpha-2/delta and beta subunits in a 1:1:1 ratio. The S3-S4 linkers of Cav1.2 determine the gating phenotype and modulated gating kinetics of the channel. Cav1.2 is widely expressed in the smooth muscle, pancreatic cells, fibroblasts, and neurons. However, it is particularly important and well known for its expression in the heart where it mediates L-type currents, which causes calcium-induced calcium release from the ER Stores via ryanodine receptors. It depolarizes at -30mV and helps define the shape of the action potential in cardiac and smooth muscle. The protein encoded by this gene binds to and is inhibited by dihydropyridine. In the arteries of the brain, high levels of calcium in mitochondria elevates activity of nuclear factor kappa B NF-κB and transcription of CACNA1c and functional Cav1.2 expression increases. Cav1.2 also regulates levels of osteoprotegerin.

Ca_V1.2 is inhibited by the action of STIM1.

Regulation

The activity of CaV1.2 channels is tightly regulated by the Ca2+ signals they produce. An increase in intracellular Ca2+ concentration implicated in Cav1.2 facilitation, a form of positive feedback called Ca2+-dependent facilitation, that amplifies Ca2+ influx. In addition, increasing influx intracellular Ca2+ concentration has implicated to exert the opposite effect Ca2+ dependent inactivation. These activation and inactivation mechanisms both involve Ca2+ binding to calmodulin (CaM) in the IQ domain in the C-terminal tail of these channels. Cav1.2 channels are arranged in cluster of eight, on average, in the cell membrane. When calcium ions bind to calmodulin, which in turn binds to a Cav1.2 channel, it allows the Cav1.2 channels within a cluster to interact with each other. This results in channels working cooperatively when they open at the same time to allow more calcium ions to enter and then close together to allow the cell to relax.

File:Ca1.2channelclutsering.png

Due to simplicity only two Calcium channels are shown to depict clustering. When depolarization occurs, calcium ions flow through the channel and some bind to Calmodulin. The Calcium/Calmodulin binding to the C-terminal pre-IQ domain of the Cav1.2 channel promotes interaction between channels that are beside each other.

Clinical significance

Mutation in the CACNA1C gene, the single-nucleotide polymorphism located in the third intron of the Cav1.2 gene, are associated with a variant of Long QT syndrome called Timothy's syndrome and also with Brugada syndrome. A large-scale genetic analysis conducted in 2008 shows the possibility that CACNA1C is associated with bipolar disorder and subsequently also with schizophrenia. Also, CACNA1C A risk allele has been associated to a disruption in brain connectivity in patients with bipolar disorder, while not or only to a minor degree, in their unaffected relatives or healthy controls.

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective Wikipedia articles.

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Nicotine Activity on Chromaffin Cells edit

See also

• Calcium channel

External links

• GeneReviews/NIH/NCBI/UW entry on Brugada syndrome
• CACNA1C protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
• GeneReviews/NIH/NCBI/UW entry on Timothy Syndrome

This article incorporates text from the United States National Library of Medicine, which is in the public domain.