voltage-dependent Ca+2 channel alpha-1A (voltage-dependent Ca+2 channel-alpha 1 isoform 4, L type, CACNA1A, CACNL1A4, CACH4, CACN3)

Function

• pore-forming & voltage-sensitive alpha-1 subunit of voltage-sensitive Ca+2 channel
• alpha-1A gives rise to P &/or Q-type Ca+2 currents; P/Q-type Ca+2 channels
  • belong to the 'high-voltage activated' (HVA) group
  • blocked by the funnel toxin (Ftx) & by the omega-agatoxin-IVA (omega-Aga-IVA)
  • insensitive to dihydropyridines (DHP), & omega-conotoxin-GVIA (omega-CTx-GVIA)

Structure

• each of the 4 internal repeats contains five 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 a series 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

membrane

Alternative splicing

named isoforms=7 Additional isoforms seem to exist

Expression

• brain specific
• mainly found in cerebellum, cerebral cortex, thalamus & hypothalamus
• no expression in heart, kidney, liver or muscle
• Purkinje cells contain predominantly P-type VSCC; the Q-type is a prominent Ca+2 current in cerebellar granule cells

Pathology

• mutations associated with:
  • familial hemiplegic migraine 1
  • spinocerebellar ataxia type-6
  • episodic ataxia type 2

Polymorphism

• the poly-Gln region of CACNA1A is polymorphic: 6-17 repeats in the normal population; expanded to ~21-30 repeats in spinocerebellar ataxia type-6; repeat expansion also reported in episodic ataxia type 2

Laboratory

• CACNA1A gene CAG repeats in blood/tissue

More general terms

• voltage-dependent Ca+2 channel alpha-1

Additional terms

• spinocerebellar ataxia type 6 (SCA-6)
• voltage-dependent Ca+2 channel

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=773
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:773
• OMIM: https://mirror.omim.org/entry/108500
• OMIM: https://mirror.omim.org/entry/141500
• OMIM: https://mirror.omim.org/entry/183086
• OMIM: https://mirror.omim.org/entry/601011
• UniProt: http://www.uniprot.org/uniprot/O00555.html