CaV2.1 | voltage-dependent, P type, alpha 1A subunit calcium channel
Family:
Calcium channels
Subgroups:
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)
Topology:
Six transmembrane alpha helices (S1–S6), total of four homologous domains make up the tetrameric alpha subunit structure
Assembling:
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
CaV2.1: Background Information
CaV2.1, also known as brain calcium channel I, gives rise to P and/or Q-type calcium currents and is predominantly expressed in neuronal tissue. Localized to the presynaptic membrane of many types of neurons, CaV2.1 ion channels are involved in triggering neurotransmitter release via both, vesicle release and postsynaptic calcium entry.
Gene:
CACNA1A
Human Protein:
UniProt O00555
Tissue:
Brain
Function/ Application:
Pre-synaptic Ca2+ influx and neurotransmitter release in neurons, fast synaptic transmission
Pathology:
Migraine (FHM-1), ataxia (EA-2, SCA6), Benign paroxysmal torticollis of infancy, hemiplegia
Interaction:
β4 subunit CACNB4, α2δ subunits, calmodulin, CaBP1, VILIP, mint, CASK, Syntaxin, SNAP25
Modulator:
Kuratoxin, ω-agatoxin IIIA, ω-conotoxin MVIIC, ω-agatoxin-IVA, roscovitine
Assays:
Patch Clamp: whole cell, room temperature
Particularities:
CaV channels often show a rundown phenomenon. Adequate intra- and extrcellular solutions are essential for a good data quality.
Recommended Reviews:
Catterall WA, Perez-Reyes E, Snutch TP, Striessnig J (2005). "International Union of Pharmacology. XLVIII. Nomenclature and structure-function relationships of voltage-gated calcium channels". Pharmacol Rev. 57 (4): 411–25.
Publications
2013 - Establishment of a Secondary Screening Assay for P/Q-Type Calcium Channel Blockers
Patchliner publication in Combinatorial Chemistry & High Throughput Screening (2013)
Authors:
Hermann D., Mezler M., Swensen A., Bruehl C., Obergrußberger A., Wicke K., Schoemaker H., Gross G., Draguhn A., Nimmrich V.