CaV1.3 | voltage-dependent, L type, alpha 1D 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
CaV1.3 Background Information
Overview:
L-type voltage gated Ca2+ channels (LTCCs) are widely expressed within different brain regions including the hippocampus. The isoforms CaV1.2 and CaV1.3 have been shown to be involved in hippocampus-dependent learning and memory, cognitive functions that require proper hippocampal neurogenesis. It is proposed that CaV1.2 channels contribues in spatial memory formation, whereas CaV1.3 channels seem to be involved in the consolidation of fear memories and in neurodegenerative mechanisms associated with the development of Parkinson's disease. Furthermore, CaV1.3 is expressed in adrenal chromaffin cells. Besides shaping the action potential (AP), the ion channels are involved in the excitation-secretion coupling controlling catecholamine release and in Ca 2+ -dependent vesicle retrieval. In pancreatic island cell, CaV1.3 is involved in the initiation of the insulin release from rat islet β cells.
Data Sheet:
Genes:
CACNA1D
Human Protein:
UniProt Q01668
Tissue:
Pancreatic islets, brain, chromaffin cells
Function/ Application:
Ca2+ entry in excitable cells
Pathology:
Sinoatrial node dysfunction, deafness, Parkinson's disease, primary aldosteronism, seizures, neurologic abnormalities, epilepsy, cancer, congenital stationary night blindness
Interaction:
CaV2.2, β1-4 subunits, α2δ subunits, ATPase Na+/K
Modulator:
Verapamil, amlodipine, isradipine, nitrendipine, felodipine, omega-agatoxin, omega-conotoxin (+-) Bay K 8644, amlodipine, diltiazem
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.
Reviews and Links
Recommended Reviews:
Transporter classification database:
UniProt:
IUPHAR/PBS:
Application Notes
Publications
2018 - Mechanism-specific assay design facilitates the discovery of Nav1.7-selective inhibitors
SyncroPatch 768PE (a predecessor model of the SyncroPatch 384/768i) publication in PNAS
Authors:
Chernov-Rogan T., Li T., Lu G., Verschoof H., Khakh K., Jones S.W., Beresini M.H., Liu C., Ortwine D.F., McKerrall S.J., Hackos D.H., Sutherlin D., Cohen C.J., and Chen J.