Target intelligence / Profile preview

Voltage-dependent L-type calcium channel subunit alpha-1D (CACNA1D) (CACNA1D)

Target
CACNA1D
Molecular classification
Ion channel, Voltage-gated calcium channel, L-type calcium channel
01

Overview

Voltage-dependent L-type calcium channel subunit alpha-1D (CACNA1D), also known as Cav1.3, is a pore-forming subunit of L-type voltage-gated calcium channels that mediates the entry of calcium ions into cells upon membrane depolarization [1, 2]. It is primarily expressed in the brain, heart (specifically the sinoatrial node), and endocrine tissues such as the adrenal glands and pancreas [1, 3]. Unlike the closely related Cav1.2 channel, Cav1.3 activates at lower voltages, making it a key regulator of neuronal excitability and cardiac pacemaking [3]. Mutations in CACNA1D are associated with several disorders, including primary aldosteronism, sinoatrial node dysfunction and deafness (SANDD) syndrome, and neurodevelopmental conditions like autism and bipolar disorder [2, 4]. Pharmacologically, Cav1.3 is targeted by L-type calcium channel blockers (CCBs) such as nifedipine and isradipine, which are used to treat hypertension, though these drugs often lack selectivity over Cav1.2 [5]. Research is currently exploring Cav1.3-selective inhibitors as potential neuroprotective agents for Parkinson's disease and for the treatment of neuropsychiatric disorders [3, 5].

Other names
Cav1.3CACN4CCHL1A2Calcium channel, L type, alpha-1 polypeptide, isoform 2SANDDPASNA
02

Mechanism of action

Inhibition of voltage-gated L-type calcium channels to reduce calcium influx into cells.

03

Biological functions

Calcium ion transportSignal transductionNeurotransmitter releaseHormone secretionCardiac pacemakingRegulation of gene expression
04

Disease associations

Primary aldosteronismSinoatrial node dysfunction and deafness (SANDD)Autism spectrum disorderParkinson's diseaseHypertensionBipolar disorderSeizure
05

Safety considerations

HypotensionBradycardiaCardiac conduction abnormalitiesPotential cognitive or neurological effects due to CNS expression
06

Interacting drugs

Nifedipine

4 more in the full profile.

07

Biomarkers

Plasma aldosterone-to-renin ratioSinoatrial node rhythmCACNA1D mutation status

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