Cav2s

Cav2s refers to the voltage-gated calcium channel subfamily Cav2, which includes Cav2.1 (P/Q-type), Cav2.2 (N-type), and Cav2.3 (R-type). Each is formed by the pore-forming alpha1 subunit encoded by CACNA1A, CACNA1B, and CACNA1E, respectively. These channels are high-voltage-activated and open in response to membrane depolarization to mediate calcium influx necessary for fast synaptic transmission.

Molecularly, the alpha1 subunit provides the ion-conducting pore and primary gating; it associates with auxiliary beta subunits (CACNB1-4) and alpha2delta subunits (CACNA2D1-4). These auxiliary subunits modulate trafficking to the membrane, expression levels, and biophysical properties such as activation and inactivation kinetics.

Distribution and function vary by subtype. Cav2.1 is abundant in cerebellar and cortical neurons and is important for neurotransmitter release at many central synapses. Cav2.2 is prominent in spinal cord and brainstem pathways and plays a key role in nociceptive signaling. Cav2.3 has a broader distribution in brain and peripheral tissues. Collectively, Cav2 channels mediate presynaptic calcium influx that triggers neurotransmitter release and contribute to synaptic plasticity and neuronal signaling.

Pharmacology and clinical relevance: Cav2 channels are targeted by specific toxins, such as agatoxins for Cav2.1 and conotoxins for Cav2.2. Gabapentinoids bind to the alpha2delta subunits and modulate Cav2 currents. Ziconotide, a Cav2.2-selective blocker delivered intrathecally, is used for severe chronic pain. Pathogenic variants in CACNA1A, CACNA1B, or CACNA1E have been associated with a range of neurological disorders, including migraine, ataxia, and epilepsy.