Inhibition of neuronal nicotinic acetylcholine receptors by La(3+).
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.
Rangel-González
Francisco J
FJ
Centro de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla, Apartado Postal 1-1141, Juriquilla, Querétaro 76001, Mexico.
García-Colunga
Jesús
J
Miledi
Ricardo
R
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D007811:Lanthanum / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008845:Microinjections; D009474:Neurons / Q000378:metabolism*; D009865:Oocytes; D018075:RNA, Complementary / Q000008:administration & dosage / Q000235:genetics; D051381:Rats; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D014981:Xenopus
D018075:RNA, Complementary; D011978:Receptors, Nicotinic; D007811:Lanthanum; D000109:Acetylcholine