α‐Conotoxin ImI Inhibits the α‐Bungarotoxin‐Resistant Nicotinic Response in Bovine Adrenal Chromaffin Cells

The activity of α‐conotoxin (α‐CTX), ImI, from the vermivorous marine snail Conus imperialis , has been studied on mammalian nicotinic receptors on bovine chromaffin cells and at the rat neuromuscular junction. Synthetic α‐CTX ImI was a potent inhibitor of the neuronal nicotinic response in bovine adrenal chromaffin cells (IC 50 = 2.5 μ M , log IC 50 = 0.4 ± 0.07), showing competitive inhibition of nicotine‐evoked catecholamine secretion. α‐CTX ImI also inhibited nicotine‐evoked 45 Ca 2+ uptake but not 45 Ca 2+ uptake stimulated by 56 m M K + . In contrast, α‐CTX ImI had no effect at the neuromuscular junction over the concentration range 1‐20 μ M . Bovine chromaffin cells are known to contain the α3β4, α7, and (possibly) α3β4α5 subtypes. However, the secretory response of bovine chromaffin cells is not inhibited by α‐bungarotoxin, indicating that α7 nicotinic receptors are not involved. We propose that α‐CTX ImI interacts selectively with the functional (α3β4 or α3β4α5) nicotinic acetylcholine receptor to inhibit the neuronal‐type nicotinic response in bovine chromaffin cells.