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+ Transporting Subunit Alpha 1, ATPase Sarcoplasmic/Endoplasmic Reticulum Ca2+ Transporting 2, CABP1, CABP4, RIMBP2, alpha-actinin, ankyrin, calmodulin,

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 extracellular solutions are essential for a good data quality.

Reviews and Links

Application Notes

CaV1.3 - Characterization of CaV1.3 on Nanion's SyncroPatch 96

icon sp96   SyncroPatch 96 (a predecessor model of the SyncroPatch 384PE) application note:  logo pdf   (0.5 MB)

Publications

2018 - Mechanism-specific assay design facilitates the discovery of Nav1.7-selective inhibitors

icon sp96  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.

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