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 inactivated rapidly (τ ~20 ms at 0 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.