Low-affinity Ca(2+) and Ba(2+) binding sites in the pore of alpha7 nicotinic acetylcholine receptors.
alpha7 nicotinic receptors are highly permeable to Ca(2+) as well as monovalent cations. We extended the characterization of the Ca(2+) permeation of non-desensitizing chick alpha7 receptors (S240T/L247T alpha7 nAChRs) expressed in Xenopus oocytes by (1) measuring the concentration dependence of conductance under conditions in which Ca(2+) or Ba(2+) were the only permeant cations in the extracellular solution, and (2) measuring the concentration dependence of Ca(2+) block of K(+) currents through the receptors. The first set of experiments yielded an apparent affinity of 0.96 mM Ca(2+) activity (2.4 mM concentration) for Ca(2+) permeation and an apparent affinity of 0.65 mM Ba(2+) activity (1.7 mM concentration) for Ba(2+) permeation. The apparent affinity of Ca(2+) inhibition of K(+) currents was 0.49 mM activity (1.5 mM concentration). The similarity of these apparent affinities in the millimolar range suggests that the pore of alpha7 receptors has one or more low-affinity Ca(2+) binding sites and no high-affinity sites.
Lyford
L K
LK
Department of Pharmacology, CB #7365, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Lee
J W
JW
Rosenberg
R L
RL
D000818:Animals; D001464:Barium / Q000737:chemistry*; D001665:Binding Sites; D002118:Calcium / Q000737:chemistry*; D002413:Cations, Divalent; D002645:Chickens; D007473:Ion Channels / Q000187:drug effects; D009154:Mutation; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009865:Oocytes / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D014981:Xenopus
D002413:Cations, Divalent; D007473:Ion Channels; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D001464:Barium; D002118:Calcium