High-voltage-activated calcium channel (HVCC) (HVCC)

High-voltage-activated (HVA) calcium channels are a family of transmembrane proteins that open in response to significant membrane depolarization to allow the influx of calcium ions into the cell (Catterall, 2011). This class is subdivided into L-type (Cav1.1-1.4), P/Q-type (Cav2.1), N-type (Cav2.2), and R-type (Cav2.3) channels, which are distinguished by their alpha-1 subunit composition and pharmacological sensitivity (Zamponi et al., 2015). These channels are essential for converting electrical signals into physiological actions, including the contraction of cardiac and smooth muscle, the release of neurotransmitters at synaptic terminals, and the secretion of hormones like insulin (Striessnig et al., 2014). Clinically, HVA channels are major targets for treating cardiovascular conditions; for example, L-type calcium channel blockers like amlodipine and verapamil are standard therapies for hypertension and arrhythmias (StatPearls, 2023). Additionally, N-type channels are targeted by drugs like ziconotide for the management of severe chronic pain, while the alpha-2-delta auxiliary subunits of HVA channels are the primary targets for gabapentinoids used in epilepsy and neuropathic pain (Bauer et al., 2007). Dysregulation or genetic mutations in these channels are linked to a variety of disorders known as channelopathies, including Lambert-Eaton myasthenic syndrome and certain forms of ataxia (Heyes et al., 2015).

Other names

High-voltage-gated calcium channelHVA calcium channelVoltage-dependent calcium channelVDCCHigh-voltage-gated Ca2+ channels

Inhibition of calcium ion influx through the channel pore or modulation of channel gating and trafficking via auxiliary subunits.