CaV1.2 | voltage-dependent, L type, alpha 1C subunit calcium channel
L-Type (CaV1.1–CaV1.4), P/Q-Type (CaV2.1), N-Type (CaV2.2), R-Type (CaV2.3), T-Type (CaV3.1–CaV3.3)
Six transmembrane alpha helices (S1–S6), total of four homologous domains make up the tetrameric alpha subunit structure
One large alpha subunit forms a functional channel, accessory subunits ( α1, α2δ, β1-4, and γ) are crucial for robust expression, they functionally modulate the alpha subunit
CaV1.2 Background Information
CaV1.2 is a subunit of L-type voltage-dependent calcium channel. In the heart it forms a complex with the subunits β2 and α2δ1 in a 1:1:1 ratio. The alpha-1 consists of 24 transmembrane segments and is the pore forming element through which ions pass into the cell, whereas the β2 and α2δ1 subunits modulate the channel function. 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 -30 mV and helps define the shape of the action potential in cardiac and smooth muscle. CaV1.2 is inhibited by the action of STIM1.
Heart, brain, lymphocytes, prostate, bladder, uterus ,stomach, colon, placenta, adrenal gland
Ca2+ entry in excitable cells
Arterial hypertension, Long QT syndrome, schizophrenia, Timothy syndrome, BRGDA3, bipolar disorder, schizophrenia
Kir/Gem, CSN5/Jab1, β1-4 subunits, α2δ subunits, NF-κB, osteoprotegerin
Verapamil, nifedipine, kurtoxin, calcicludine, mibefradil, calciseptine, BAYK-8644, verapamil
Patch Clamp: whole cell, room temperature
CaV channels often show a rundown phenomenon. Adequate intra- and extracellular solutions are essential for a good data quality.
Reviews and Links
- Catterall et al. (2005) International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels. Pharmacol Rev. 57 (4): 411–25.