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Vol. 55, Issue 1, 58-66, January 1999
4
2 Receptors
Stably Expressed in HEK293 Cells
Department of Anesthesiology, Washington University School of
Medicine, St. Louis, Missouri
HEK293 cells were stably transfected with rat neuronal nicotinic 
4
and 
2 subunits. Binding of tritiated cytisine and nicotine to cell
homogenates revealed the presence of a single class of high-affinity
sites (dissociation constants 0.1 nM and 0.4 nM, respectively).
Activation of nicotinic receptors was studied using whole-cell patch
clamp methods, and acetylcholine, nicotine, dimethylphenylpiperazinium, and cytisine all produced a conductance increase. Responses
desensitized to prolonged applications, at both positive and negative
membrane potentials. The conductance was strongly rectifying, and
outward currents were essentially absent. Responses were maximal at
about 2 mM external calcium ion concentration and were reduced by about one-half at either nominally 0 or 10 mM external calcium.
Di-hydro--erythroidine blocked physiological responses to
acetylcholine and nicotine (IC50, 2.5 nM), and reduced
cytisine binding in a competitive manner (Ki
20 nM). Physostigmine enhanced the response to low concentrations of
acetylcholine or nicotine. The anesthetic steroid (+)-3-hydroxy-5-androstane-17-carbonitrile blocked responses to acetylcholine (IC50, 1.3 µM), but had no effect on
cytisine binding at a concentration of 30 µM. The binding properties
of the receptors are those expected for rat neuronal nicotinic
receptors composed of 4 and 2 subunits. The pharmacological
properties indicate that the responsiveness of the receptors may be
allosterically enhanced or inhibited.
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