voltage-dependent Ca+2 channel alpha-1D; Ca+2 channel L type alpha-1 polypeptide isoform 2; Cav1.3 (CACNA1D CACNL1A2, CCHL1A2, CACH3, CACN4)
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Function
- pore-forming & voltage-sensitive alpha-1 subunit of voltage-sensitive Ca+2 channel
- alpha-1D gives rise to L-type Ca+2 currents;
- long-lasting (L-type) Ca+2 channels belong to the 'high-voltage activated' (HVA) group
- blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, & by omega-agatoxin-IIIA (omega-Aga-IIIA)
- insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) & omega-agatoxin-IVA (omega-Aga-IVA)
- alpha-1D subunit is sufficient to generate voltage-sensitive Ca+2 channel activity
- interacts with RIMBP2 (putative)
Structure
- each of the 4 internal repeats contains 5 hydrophobic transmembrane segments (S1, S2, S3, S5, S6) & one positively charged transmembrane segment (S4).
- S4 segments probably represent the voltage-sensor; they are characterized by aseries of positively charged amino acids at every third position
- belongs to the Ca+2 channel alpha-1 subunit (TC 1.A.1.11) family
Compartment
presynpatic membrane
Alternative splicing
named isoforms=2
Expression
- expressed in pancreatic islets & in brain
- in brain, expressed in hippocampus, basal ganglia, habenula & thalamus
- no expression in skeletal muscle
Pathology
- associated with paraneoplastic autoantibody anti-Vgcc
Polymorphism
- a change from 7 to 8 ATG trinucleotide repeats, resulting in an additional N-terminal Met, has been found in a patient with non-insulin-dependent diabetes mellitus (NIDDM)