High-voltage-activated voltage-gated calcium channel (HVA VGCC)

High-voltage-activated (HVA) voltage-gated calcium channels are critical mediators of sensory transmission in dental afferent neurons, which primarily originate from the trigeminal ganglion (Borgland et al., 2001, PubMed). These channels, including the Cav1 (L-type) and Cav2 (N, P/Q, and R-type) families, open in response to strong membrane depolarization to allow calcium influx (Catterall, 2011, Cold Spring Harb Perspect Biol). This influx triggers the exocytosis of pro-nociceptive neurotransmitters such as Substance P and calcitonin gene-related peptide (CGRP) from the central and peripheral terminals of dental primary afferents (Gibbs et al., 2004, Neuroscience). In pathological states like pulpitis or dental nerve injury, the expression and function of these channels are often upregulated, leading to peripheral sensitization and chronic dental pain (Park et al., 2015, J Dent Res). Pharmacological agents such as gabapentinoids (gabapentin and pregabalin) target the alpha-2-delta auxiliary subunits of these HVA channels to reduce neurotransmitter release and alleviate neuropathic pain (Field et al., 2006, Nat Rev Neurosci). Additionally, specific blockers of N-type (e.g., ziconotide) and L-type channels are utilized or studied for their ability to modulate the excitability of nociceptive pathways in the trigeminal system (Zamponi et al., 2015, Nat Rev Neurosci).

Other names

HVA Ca2+ channelsHigh-threshold calcium channelsCav1 and Cav2 calcium channelsVoltage-dependent calcium channelsHVA VGCCs

Inhibition of calcium influx through high-voltage-activated channels, thereby reducing the release of excitatory neurotransmitters (e.g., glutamate, CGRP, Substance P) and decreasing the excitability of sensory neurons in the trigeminal system (Zamponi et al., 2015, Nat Rev Neurosci; Field et al., 2006, Nat Rev Neurosci).