Molecular analysis and functional expression of the human type E neuronal Ca2+ channel alpha 1 subunit. Academic Article uri icon

Overview

abstract

  • A human brain alpha 1 Ca2+ channel subunit was cloned and expressed in Xenopus laevis oocytes. The open reading frame, encoding 2,312 amino acids, has high homology to the marine ray doe-1, the rat E-type, and the rabbit brain BII alpha 1 subunits. The amino and carboxy termini of this human.E-type alpha 1 subunit (alpha 1E) are most similar to the rabbit BII-1 splice variant, the remainder being colinear with the BII alpha 1 with the exception of two insertions, one of 43 amino acids in the C-terminus and another of 7 amino acids, found also in the rat alpha 1E, between domains II and III. Two potential Ca2+ binding sites are predicted from its primary structure. The expression of inward Ba2+ currents reveals voltage-dependent activation and inactivation measured by the cut-open oocyte vaseline-gap technique, with kinetics that correspond to that of a high-voltage-activated neuronal Ca2+ channel, and pharmacologic properties that resemble those of some low-voltage-activated neuronal Ca2+ currents. The human alpha 1E currents are insensitive to omega-conotoxin-GVIA (1 microM), omega-agatoxin-IVA (200 nM), a synthetic funnel web spider toxin (FTX, 20 microM), and Bay-K8644 (0.5 microM); they are inhibited 20% by high concentrations of methoxyverapamil and diltiazem, 65% by 0.1% crude funnel web spider venom and 100% by Ni2+ (IC50 = 30 nM). Single-channel records show a complex activity pattern with several apparent conductance states, the largest having a conductance of 14 pS.

authors

  • Appel, Stanley
  • Schneider, T
  • Wei, X
  • Olcese, R
  • Costantin, J L
  • Neely, A
  • Palade, P
  • Perez-Reyes, E
  • Qin, N
  • Zhou, J
  • Crawford, G D

publication date

  • January 1, 1994

Research

keywords

  • Brain
  • Calcium Channels
  • Cation Transport Proteins
  • Gene Expression
  • Neurons
  • Oocytes

Identity

Scopus Document Identifier

  • 0028658348

PubMed ID

  • 7536609

Additional Document Info

volume

  • 2

issue

  • 4