Analogies and differences between omega-conotoxins MVIIC and MVIID: binding sites and functions in bovine chromaffin cells

Pflugers Arch. 1997 Dec;435(1):55-64. doi: 10.1007/s004240050483.


The characteristics of the binding sites for the Conus magus toxins omega-conotoxin MVIIC and omega-conotoxin MVIID, as well as their effects on K+-evoked 45Ca2+ entry and whole-cell Ba2+ currents (IBa), and K+-evoked catecholamine secretion have been studied in bovine adrenal chromaffin cells. Binding of [125I] omega-conotoxin GVIA to bovine adrenal medullary membranes was displaced by omega-conotoxins GVIA, MVIIC and MVIID with IC50 values of around 0.1, 4 and 100 nM, respectively. The reverse was true for the binding of [125I] omega-conotoxin MVIIC, which was displaced by omega-conotoxins MVIIC, MVIID and GVIA with IC50 values of around 30, 80 and 1.200 nM, respectively. The sites recognized by omega-conotoxins MVIIC and MVIID in bovine brain exhibited higher affinities (IC50 values of around 1 nM). Both omega-conotoxin MVIIC and MVIID blocked IBa by 70-80%; the higher the [Ba2+]o of the extracellular solution the lower the blockade induced by omega-conotoxin MVIIC. This was not the case for omega-conotoxin MVIID; high Ba2+ (10 mM) slowed down the development of blockade but the maximum blockade achieved was similar to that obtained in 2 mM Ba2+. A further difference between the two toxins concerns their reversibility; washout of omega-conotoxin MVIIC did not reverse the blockade of IBa while in the case of omega-conotoxin MVIID a partial, quick recovery of current was produced. This component was irreversibly blocked by omega-conotoxin GVIA, suggesting that it is associated with N-type Ca2+ channels. Blockade of K+-evoked 45Ca2+ entry produced results which paralleled those obtained by measuring IBa. Thus, 1 microM of each of omega-conotoxin GVIA and MVIIA inhibited Ca2+ uptake by 25%, while 1 microM of each of omega-conotoxin MVIIC and MVIID caused a 70% blockade. K+-evoked catecholamine secretory responses were not reduced by omega-conotoxin GVIA (1 microM). In contrast, at 1 microM both omega-conotoxin MVIIC and MVIID reduced the exocytotic response by 70%. These data strengthen the previously established conclusion that Q-type Ca2+ channels that contribute to the regulation of secretion and are sensitive to omega-conotoxins MVIIC and MVIID are present in bovine chromaffin cells. These channels, however, seem to possess binding sites for omega-conotoxins MVIIC and MVIID whose characteristics differ considerably from those described to occur in the brain; they might represent a subset of Q-type Ca2+ channels or an entirely new subtype of voltage-dependent high-threshold Ca2+ channel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Medulla / metabolism*
  • Animals
  • Barium / metabolism
  • Binding Sites
  • Binding, Competitive
  • Brain / metabolism
  • Calcium / metabolism
  • Calcium Channel Blockers / metabolism*
  • Calcium Channel Blockers / pharmacology
  • Catecholamines / metabolism
  • Cattle
  • Cell Membrane / metabolism
  • Chromaffin System / metabolism*
  • Conotoxins*
  • Electric Conductivity
  • Kinetics
  • Peptides / metabolism*
  • Peptides / pharmacology
  • Potassium / pharmacology
  • omega-Conotoxin GVIA
  • omega-Conotoxins*


  • Calcium Channel Blockers
  • Catecholamines
  • Conotoxins
  • Peptides
  • omega-Conotoxins
  • omega-conotoxin-MVIIC
  • omega-conotoxin MVIID
  • Barium
  • omega-Conotoxin GVIA
  • Potassium
  • Calcium