Cav2, a group of voltage-gated calcium channels, includes subtypes such as Cav2.1 (P/Q-type), Cav2.2 (N-type), and Cav2.3 (R-type). These channels play a crucial role in processes like synaptic transmission, neuronal excitability, and pain signaling. For instance, Cav2.1 channels are involved in regular pace-making activity of Purkinje cells in the cerebellum [3]. The CACNA1A gene encodes the pore-forming alpha1 subunit of Cav2.1 channels, and mutations in this gene can cause autosomal-dominant neurologic disorders like familial hemiplegic migraine type 1 (FHM1), episodic ataxia type 2, and spinocerebellar ataxia type 6 (SCA6) [1].

In FHM1 knockin mouse models, FHM1-causing mutations in Cav2.1 channels have been shown to affect cortical spreading depression, which is related to migraine aura, as well as cortical excitatory and inhibitory synaptic transmission [1]. Different ataxic spontaneous cacna1a mouse mutants have provided insights into the cerebellar mechanisms underlying motor dysfunction caused by mutant Cav2.1 channels [1]. Regarding Cav2.3, studies using rodent pain models suggest it has a pro-nociceptive role in pain, and its activity or expression reduction can impact pain signaling [2].

In conclusion, Cav2 channels are essential for normal neuronal and synaptic function. Research using gene-modified mouse models, such as knockin and spontaneous mutants, has significantly enhanced our understanding of the role of Cav2 channels in neurological disorders like migraines and ataxias, as well as in pain-related processes. These models have provided valuable insights into the underlying mechanisms, which may help in developing new therapeutic strategies for these diseases.

References:

1. Pietrobon, Daniela. 2010. CaV2.1 channelopathies. In Pflugers Archiv : European journal of physiology, 460, 375-93. doi:10.1007/s00424-010-0802-8. https://pubmed.ncbi.nlm.nih.gov/20204399/

2. de Amorim Ferreira, Marcella, Ferreira, Juliano. . Role of Cav2.3 (R-type) Calcium Channel in Pain and Analgesia: A Scoping Review. In Current neuropharmacology, 22, 1909-1922. doi:10.2174/1570159X21666230811102700. https://pubmed.ncbi.nlm.nih.gov/37581322/

3. Folacci, Mathilde, Estaran, Sébastien, Ménard, Claudine, Charnet, Pierre, Cens, Thierry. 2023. Functional Characterization of Four Known Cav2.1 Variants Associated with Neurodevelopmental Disorders. In Membranes, 13, . doi:10.3390/membranes13010096. https://pubmed.ncbi.nlm.nih.gov/36676903/