Inhibition of neuronal nicotinic acetylcholine receptors by La(3+)

Abstract

A study was made of the effects of La(3+) on neuronal alpha 2 beta 4 nicotinic acetylcholine receptors expressed in Xenopus oocytes. La(3+) by itself (up to 10 microM) did not elicit significant membrane currents. However, La(3+) reversibly inhibited the ionic currents induced by acetylcholine (IC(50)=13.5+/-4.3 microM). When La(3+) and acetylcholine were simultaneously applied onto an oocyte, the level of inhibition of the acetylcholine response was the same as when the oocyte was first preincubated with La(3+) and then exposed to acetylcholine plus La(3+). In the presence of La(3+), the EC(50) decreased from 43.8+/-6.4 to 26.5+/-5.1 microM, suggesting a small increase in the affinity of acetylcholine for the receptors through a noncompetitive mechanism. The inhibition of acetylcholine response was independent of the membrane potential. From these results we conclude that La(3+) regulates nicotinic receptors, reversibly and noncompetitively, presumably by inhibiting allosterically the receptor through interactions at an external domain of the receptor complex.