Cav2 refers to a group of voltage-gated calcium channels, including CaV2.1 (P/Q-type), CaV2.2 (N-type), and CaV2.3 (R-type) channels. These channels play crucial roles in processes such as synaptic transmission, pain signaling, and neuronal excitability. They are encoded by genes like CACNA1A (for CaV2.1), CACNA1B (for CaV2.2), and CACNA1E (for CaV2.3). Genetic models, especially knockout (KO) mouse models, are valuable for studying their functions [1,2,3].

Mutations in the CACNA1A gene encoding CaV2.1 channels cause autosomal-dominant neurologic disorders such as familial hemiplegic migraine type 1 (FHM1), episodic ataxia type 2, and spinocerebellar ataxia type 6 (SCA6). In FHM1 and SCA6 knockin mouse models, the functional consequences of disease-causing mutations on neuronal CaV2.1 channels expressed at endogenous physiological levels have been studied. For example, FHM1 mutations affect cortical spreading depression, cortical excitatory and inhibitory synaptic transmission [1]. Some studies using rodent pain models to reduce Cav2.3 activity or expression mostly demonstrated a pro-nociceptive role of Cav2.3 [3].

In conclusion, Cav2 channels are essential for normal physiological functions, especially in the nervous system. Studies using KO/CKO mouse models have revealed their roles in various neurological disorders such as FHM1, episodic ataxia type 2, and SCA6, as well as in pain signaling. Understanding the functions of Cav2 channels through these models provides insights into the mechanisms of these diseases and potential therapeutic targets.