Voltage-dependent L-type calcium channel subunit alpha-1S, alpha-1D, and alpha-1F (Cav1.1, Cav1.3, Cav1.4)

Voltage-dependent L-type calcium channels (LTCCs) Cav1.1, Cav1.3, and Cav1.4 are high-voltage-activated channels that facilitate the influx of calcium ions into excitable cells upon membrane depolarization (Striessnig et al., 2010) [1.3.1]. These channels are composed of a pore-forming alpha-1 subunit (alpha-1S, alpha-1D, and alpha-1F, respectively) and auxiliary subunits that modulate their activity (Catterall et al., 2005) [1.3.4]. Cav1.1 is essential for excitation-contraction coupling in skeletal muscle, while Cav1.3 regulates pacemaking in the heart and brain, neurotransmitter release in the inner ear, and hormone secretion (Zamponi et al., 2015) [1.3.2]. Cav1.4 is uniquely localized to the retina, where it mediates tonic neurotransmitter release at photoreceptor ribbon synapses (Morgans, 2001) [1.3.4]. Mutations in these channels lead to distinct clinical disorders, such as hypokalemic periodic paralysis (Cav1.1), sinoatrial node dysfunction and deafness (Cav1.3), and congenital stationary night blindness (Cav1.4) [1.1.1, 1.5.1]. They are the primary targets for clinically used calcium channel blockers, including dihydropyridines like nifedipine and amlodipine, which are used to manage hypertension and cardiovascular conditions (Striessnig, 2021) [1.3.2]. Beyond their established roles, Cav1.3 is currently being investigated as a therapeutic target for neuroprotection in Parkinson's disease and for the treatment of certain neuropsychiatric disorders [1.3.5].

Other names

CACNA1SCACNA1DCACNA1FL-type calcium channelsLTCCsDihydropyridine receptorDHPRCACNL1A3CACNL1A2CACH3SANDDCSNB2

Blockade of the alpha-1 subunit pore to inhibit calcium ion influx, stabilization of the inactivated state, and reduction of channel opening frequency (Striessnig, 2021) [1.3.2, 1.4.1].