Cav2.1

Cav2.1 (also known as α1A subunit) is a subunit of a voltage-dependent calcium channel. Specifically, it is the pore-forming α1 subunit of the P/Q-type voltage-gated calcium channel, classified as a high-voltage activated (HVA) channel.

Function:

Cav2.1 channels play a crucial role in neuronal excitability and synaptic transmission. They are predominantly expressed in the brain, particularly at presynaptic terminals where they mediate calcium influx required for the release of neurotransmitters. They are involved in a wide range of neurological functions, including motor coordination, learning, and memory.

Structure:

Like other α1 subunits of voltage-gated calcium channels, Cav2.1 is a large transmembrane protein consisting of four homologous domains (I-IV), each containing six transmembrane segments (S1-S6). The S4 segments act as voltage sensors. The pore region is formed by the loops connecting S5 and S6 in each domain. Auxiliary subunits, such as β and α2δ, can associate with the α1 subunit to modulate channel trafficking, expression, and biophysical properties.

Clinical Significance:

Mutations in the gene encoding Cav2.1 (CACNA1A) are associated with a variety of neurological disorders, including:

• Familial Hemiplegic Migraine Type 1 (FHM1): A severe form of migraine with aura, often accompanied by weakness on one side of the body.
• Episodic Ataxia Type 2 (EA2): A neurological disorder characterized by recurrent episodes of ataxia (lack of coordination).
• Spinocerebellar Ataxia Type 6 (SCA6): A progressive neurodegenerative disorder affecting the cerebellum.
• Other neurological disorders: Including seizures and intellectual disability, depending on the specific mutation.

The study of Cav2.1 channels is important for understanding the pathogenesis of these neurological disorders and for developing potential therapeutic strategies.