The effects of methyllycaconitine on the response of TE‐671 cells to acetylcholine and epibatidine

Methyllycaconitine (MLA) is a norditerpenoid alkaloid found in Delphinium spp., and is a potent and selective antagonist of α 7 ‐nicotinic acetylcholine receptors. Plants with high concentrations of MLA are responsible for many livestock poisonings in the Intermountain West of the United States of America. The objective of this study was to characterize the actions of MLA on the response of TE‐671 cells to two nicotinic acetylcholine receptor agonists, acetylcholine, and epibatidine. The actions of MLA were assessed by measuring changes in membrane potential sensing dye responses of TE‐671 cells expressing (α 1 ) 2 β 1 γδ nicotinic acetylcholine receptors. Changes in cell membrane potential from the addition of agonists were measured as changes in fluorescence of a membrane potential‐sensitive dye and normalized to the maximum epibatidine response. MLA at nanomolar concentrations potentiated the membrane potential sensing dye response of TE‐671 cells to acetylcholine and epibatidine. The amount of potentiation was agonist‐dependant as well as concentration‐dependant. These results suggest that the poisoning of livestock by Delphinium spp. is more complex than previously thought and that the potentiation of nicotinic acetylcholine receptors may alter the toxicity of MLA in susceptible animals.