Transfer of 1,4-dihydropyridine sensitivity from L-type to class A (BI) calcium channels

Neuron. 1996 Jan;16(1):207-18. doi: 10.1016/s0896-6273(00)80037-9.


L-type Ca2+ channels are characterized by their unique sensitivity to organic Ca2+ channel modulators like the 1,4-dihydropyridines (DHPs). To identify molecular motifs mediating DHP sensitivity, we transferred this sensitivity from L-type Ca2+ channels to the DHP-insensitive class A brain Ca2+ channel, BI-2. Expression of chimeras revealed minimum sequence stretches conferring DHP sensitivity including segments IIIS5, IIIS6, and the connecting linker, as well as the IVS5-IVS6 linker plus segment IVS6. DHP agonist and antagonist effects are determined by different regions within the repeat IV motif. Sequence regions responsible for DHP sensitivity comprise only 9.4% of the overall primary structure of a DHP-sensitive alpha 1A/alpha 1S construct. This chimera fully exhibits the DHP sensitivity of channels formed by L-type alpha 1 subunits. In addition, it displays the electrophysiological properties of alpha 1A, as well as its sensitivity toward the peptide toxins omega-agatoxin IVA and omega-conotoxin MVIIC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Calcium / metabolism*
  • Calcium Channel Agonists / pharmacology
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / chemistry*
  • Calcium Channels / drug effects*
  • Calcium Channels / genetics
  • Calcium Channels, L-Type
  • Carps
  • Dihydropyridines / pharmacology*
  • Ion Channel Gating / drug effects
  • Isradipine / pharmacology
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptides / pharmacology
  • Protein Structure, Tertiary
  • Pyrroles / pharmacology
  • Rabbits
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / drug effects*
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Spider Venoms / pharmacology
  • omega-Agatoxin IVA
  • omega-Conotoxins*


  • Calcium Channel Agonists
  • Calcium Channel Blockers
  • Calcium Channels
  • Calcium Channels, L-Type
  • Dihydropyridines
  • Peptide Fragments
  • Peptides
  • Pyrroles
  • Recombinant Fusion Proteins
  • Spider Venoms
  • omega-Agatoxin IVA
  • omega-Conotoxins
  • FPL 64176
  • omega-conotoxin-MVIIC
  • 1,4-dihydropyridine
  • Calcium
  • Isradipine