Multiple structural elements in voltage-dependent Ca2+ channels support their inhibition by G proteins

Neuron. 1996 Nov;17(5):991-1003. doi: 10.1016/s0896-6273(00)80229-9.


Molecular determinants of Ca2+ channel responsiveness to inhibition by receptor-coupled G proteins were investigated in Xenopus oocytes. The inhibitory response of alpha1B (N-type) channels was much larger than alpha1A (P/Q-type) channels, while alpha1C (L-type) channels were unresponsive. Differences in both degree and speed of inhibition were accounted for by variations in inhibitor off-rate. We tested proposals that inhibitory G protein and Ca2+ channel beta subunits compete specifically at the I-II loop. G protein-mediated inhibition remained unaltered in alpha1B subunits containing a point mutation in the I-II loop segment critical for Ca2+ channel beta subunit binding, and in chimeras where the I-II loop of alpha1B was replaced with counterparts from alpha1A or alpha1c. Full interconversion between modulatory behaviors of alpha1B and alpha1A was achieved only by swapping both motif I and the C-terminus in combination. Thus, essential structural elements for G protein modulation reside in multiple Ca2+ channel domains.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium Channel Blockers / metabolism
  • Calcium Channels / chemistry*
  • Calcium Channels / physiology*
  • Electrophysiology
  • Female
  • GTP-Binding Proteins / physiology*
  • Ion Channel Gating / physiology*
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / physiology
  • Signal Transduction / physiology
  • Time Factors
  • Xenopus


  • Calcium Channel Blockers
  • Calcium Channels
  • Recombinant Fusion Proteins
  • GTP-Binding Proteins