Cacna1a
Domain
Each of the four internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6) and one positively charged transmembrane segment (S4). S4 segments probably represent the voltage-sensor and are characterized by a series of positively charged amino acids at every third position.
Function
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1A gives rise to P and/or Q-type calcium currents. P/Q-type calcium channels belong to the 'high-voltage activated' (HVA) group and are specifically blocked by the spider omega-agatoxin-IVA (AC P54282) (By similarity). They are however insensitive to dihydropyridines (DHP).
Involvement in disease
Defects in Cacna1a are the cause of a delayed-onset, recessive neurological disorder seen in tottering (tg) mutants, resulting in ataxia, motor seizures and behavioral absence seizures resembling petit mal epilepsy (or absence epilepsy) in humans. There are two more alleles, leaner (tg(lA)), that is characterized by severe ataxia and frequent death past weaning, but no motor seizures; and rolling Nagoya (tg(rol)), that presents an intermediary phenotype, the ataxia being somewhat more severe that with tg, but without motors seizures. Selective degeneration of cerebellar Purkinje cells has been shown for all these types of mutants. Selective degeneration of cerebellar Purkinje cells has been shown for all these types of mutants.
Sequence Similarities
Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1A subfamily.
Tissue Specificity
Brain specific; mainly found in the cerebellum, olfactory bulb, cerebral cortex, hippocampus, and inferior colliculus. In the hippocampus, expression occurs in pyramidal and granule neurons, as well as in interneurons. Purkinje cells contain predominantly P-type VSCC, the Q-type being a prominent calcium current in cerebellar granule cells.
Cellular localization
- Cell membrane
- Multi-pass membrane protein
Alternative names
Caca1a, Cach4, Cacn3, Cacnl1a4, Ccha1a, Cacna1a, Voltage-dependent P/Q-type calcium channel subunit alpha-1A, Brain calcium channel I, Voltage-gated calcium channel subunit alpha Cav2.1, BI