Voltage-dependent R-type calcium channel subunit alpha-1E (CaV2.3) (CaV2.3)

Voltage-dependent R-type calcium channel subunit alpha-1E (CaV2.3) is a pore-forming subunit of R-type voltage-gated calcium channels, primarily encoded by the CACNA1E gene (UniProt: P78508). These channels are widely expressed throughout the central nervous system, where they contribute to high-voltage-activated calcium currents that regulate neurotransmitter release and synaptic plasticity (PubMed: 10366619). CaV2.3 is characterized by its "residual" (R-type) current, which remains after the pharmacological blockade of L-, N-, and P/Q-type channels. In clinical contexts, gain-of-function mutations in CACNA1E are a known cause of developmental and epileptic encephalopathy 69 (DEE69), characterized by refractory seizures and developmental delay (PubMed: 30545854). Beyond epilepsy, CaV2.3 has been implicated in the modulation of chronic pain pathways and the regulation of insulin secretion in pancreatic beta cells (PubMed: 24501221). While selective inhibitors like the peptide toxin SNX-482 exist for research, therapeutic targeting often involves non-selective anticonvulsants such as topiramate or lamotrigine (PubMed: 15121994).

Other names

CACNA1ER-type calcium channelCalcium channel, voltage-dependent, R type, alpha 1E subunitBIICav2.3

Inhibition of the alpha-1E subunit reduces high-voltage-activated R-type calcium currents, thereby modulating neuronal firing and neurotransmitter release.