Calcium voltage-gated channel subunit alpha1 D (Cav1.3) (CACNA1D)

The Calcium voltage-gated channel subunit alpha1 D, commonly known as Cav1.3, is a critical pore-forming protein that mediates the influx of calcium ions into excitable cells in response to membrane depolarization [Open Targets, NCBI]. It is widely expressed in the brain, heart, endocrine glands, and inner ear, where it regulates essential processes such as neurotransmitter release, hormone secretion, and cardiac pacemaking [Hyperinsulinism Genes, MedlinePlus, Ma'ayan Lab]. Unlike the closely related Cav1.2 channel, Cav1.3 activates at more negative (sub-threshold) potentials, allowing it to control neuronal excitability and rhythmic firing [Wikipedia, IUPHAR]. In the adrenal glands, it plays a pivotal role in the production of aldosterone, while in the pancreas, it facilitates insulin release from beta cells [Hyperinsulinism Genes, MedlinePlus]. Dysfunction of Cav1.3 is linked to several clinical conditions, including primary aldosteronism, PASNA syndrome (characterized by seizures and neurological abnormalities), and SANDD syndrome (sinoatrial node dysfunction and deafness) [MedlinePlus, JensenLab, Taylor & Francis]. Furthermore, Cav1.3-mediated calcium entry is implicated in the progressive loss of dopaminergic neurons in Parkinson's disease, making it a significant target for neuroprotective strategies [Taylor & Francis, Wikipedia]. While existing L-type calcium channel blockers like isradipine and nifedipine inhibit Cav1.3, they lack selectivity over Cav1.2, which often leads to dose-limiting cardiovascular side effects [ResearchGate, IUPHAR]. Consequently, the development of Cav1.3-selective inhibitors is a major focus for treating neuropsychiatric disorders and endocrine-related hypertension [Taylor & Francis, Journal of Cellular and Molecular Medicine].

Other names

Cav1.3CACNA1DCACH3CACN4CACNL1A2CCHL1A2Voltage-dependent L-type calcium channel subunit alpha-1DCalcium channel, L type, alpha-1 polypeptideCalcium channel, neuroendocrine/brain-type, alpha 1 subunit

Calcium channel antagonism, pore blockade, and voltage-dependent inhibition.