Molecular basis of drug interaction with L-type Ca2+ channels

J Bioenerg Biomembr. 1998 Aug;30(4):319-34. doi: 10.1023/a:1021933504909.


Different types of voltage-gated Ca2+ channels exist in the plasma membrane of electrically excitable cells. By controlling depolarization-induced Ca2+ entry into cells they serve important physiological functions, such as excitation-contraction coupling, neurotransmitter and hormone secretion, and neuronal plasticity. Their function is fine-tuned by a variety of modulators, such as enzymes and G-proteins. Block of so-called L-type Ca2+ channels by drugs is exploited as a therapeutic principle to treat cardiovascular disorders, such as hypertension. More recently, block of so-called non-L-type Ca2+ channels was found to exert therapeutic effects in the treatment of severe pain and ischemic stroke. As the subunits of different Ca2+ channel types have been cloned, the modulatory sites for enzymes, G-proteins, and drugs can now be determined using molecular engineering and heterologous expression. Here we summarize recent work that has allowed us to determine the sites of action of L-type Ca2+ channel modulators. Together with previous biochemical, electrophysiological, and drug binding data these results provide exciting insight into the molecular pharmacology of this voltage-gated Ca2+ channel family.

Publication types

  • Review

MeSH terms

  • Affinity Labels
  • Allosteric Regulation
  • Allosteric Site
  • Amino Acid Sequence
  • Animals
  • Antibody Specificity
  • Antihypertensive Agents / pharmacology
  • Binding Sites
  • Calcium / metabolism
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels / chemistry
  • Calcium Channels / drug effects*
  • Calcium Channels / genetics
  • Calcium Channels / immunology
  • Calcium Channels, L-Type
  • Calcium Signaling / drug effects
  • Drug Design
  • Epitopes / immunology
  • Humans
  • Ion Channel Gating / drug effects
  • Models, Biological
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Protein Binding
  • Protein Conformation
  • Recombinant Fusion Proteins / metabolism
  • Structure-Activity Relationship


  • Affinity Labels
  • Antihypertensive Agents
  • Calcium Channel Blockers
  • Calcium Channels
  • Calcium Channels, L-Type
  • Epitopes
  • Recombinant Fusion Proteins
  • Calcium