Voltage-dependent R-type calcium channel (Cav2.3)

The Voltage-dependent R-type calcium channel, primarily encoded by the CACNA1E gene and known as Cav2.3, is a high-voltage-activated channel that mediates calcium entry into neurons and endocrine cells [1][2]. It is widely expressed throughout the central nervous system, particularly in the hippocampus, cortex, and striatum, where it plays a pivotal role in neurotransmitter release and synaptic plasticity [3]. Beyond the brain, Cav2.3 is involved in the regulation of insulin secretion from pancreatic beta cells and the transmission of nociceptive signals in the spinal cord [5]. Mutations in the CACNA1E gene, particularly gain-of-function variants, have been identified as a cause of severe developmental and epileptic encephalopathy (DEE69), characterized by refractory seizures and profound developmental delay [4]. The channel is also implicated in the pathogenesis of Parkinson's disease and chronic neuropathic pain, making it a significant target for therapeutic intervention [5]. While selective pharmacological tools like the peptide toxin SNX-482 exist for research, clinical drug development focuses on identifying small-molecule inhibitors to treat hyperexcitability disorders [3][5]. Sources: [1] UniProt (Q15878); [2] Pharmacol Rev (2005) 57:411-25; [3] Channels (2013) 7:4, 254-261; [4] Am J Hum Genet (2018) 103:666-678; [5] Pharmacol Rev (2015) 67:821-870.

Other names

CACNA1ECalcium channel voltage-dependent alpha 1E subunitR-type calcium channelCaV2.3BII

Inhibition of calcium ion influx through the alpha-1E pore-forming subunit to modulate neuronal firing and transmitter release [2][5].