Structure and functional characterization of neuronal α_1E calcium channel subtypes

We have cloned overlapping cDNAs encoding α_1E Ca²⁺ channel subunits from mouse and human brain. We observed that these α_1E transcripts were widely distributed in the central nervous system. We also demonstrated the existence of two variants of the human α_1E subunit. Comparison of the sequence of these α_1E subunits to those from other species suggests that at least four alternatively spliced variants of α_1E exist. Expression of human α_1E in HEK293 cells and Xenopus oocytes produced high voltage-activated Ca2+ currents that in-activated rapidly (τ ∼20 ms at O mV). The size of the currents obtained were enhanced ∼40-fold by co-expression with human neuronal α₂ and β Ca²⁺ channel subunits. α_1E currents were insensitive to the drugs and toxins previously used to define other classes of voltage-activated Ca²⁺ channels. Thus, α_1E-mediated Ca²⁺ channels appear to be a pharmacologically distinct class of voltage-activated Ca²⁺ channels.