![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 55, Issue 6, 970-981, June 1999
3/
4 Neuronal Nicotinic Acetylcholine Receptor
Department of Pharmacology, Georgetown University School of
Medicine, Washington, D.C.
The 
3/
4 rat neuronal nicotinic acetylcholine receptor, stably
transfected in human embryonic kidney cells, was examined using
the whole-cell-clamp technique and 2-dimensional confocal imaging. Application of agonists (nicotine, cytisine, epibatidine) activated a large (100-200 pA/pF) inwardly rectifying monovalent current, with little current at voltages between 0 and +40 mV. Rapid
application of nicotine and cytisine indicated EC50 values of 
22 and 64 µM, respectively, and suggested second order
binding kinetics (Hill coefficient ~2). The time constant of
desensitization (decay) of nicotine-activated current was
concentration-dependent (typically ~10 s at 30 µM versus ~1.0 s
at 100-1000 µM), but not voltage-dependent and was significantly
smaller than the ~200 s reported for the 3/4 receptor expressed
in Xenopus oocytes. Nicotine-activated current was
rapidly and reversibly blocked by coapplication of mecamylamine and
d-tubocurarine. At 
80 mV holding potentials, the
current was also suppressed by ~25% either upon complete removal or
elevation of Ca2+ to 10 mM. Total replacement of
Na+ by Ca2+ also completely blocked the
current. On the other hand, evidence for permeation of Ca2+
was indicated by increased inward current at 40 mV upon elevation of
Ca2+ from 2 to 10 mM, as well as a rise in the cytosolic
Ca2+ proportional to the current carried by the receptor.
These findings are consistent with the idea that Ca2+, in
addition to its channel-permeating properties, may also regulate the
receptor from an extracellular site. Our results suggest that the
3/4 neuronal nicotinic acetylcholine receptor, when stably expressed in human embryonic kidney 293 cells, has desensitization kinetics and Ca2+ regulatory mechanisms somewhat different
from those described for the receptor expressed in
Xenopus oocytes.
This article has been cited by other articles:
|
|
 |
|
  G. R. Abdrakhmanova, M. I. Damaj, F. I. Carroll, and B. R. Martin 2-Fluoro-3-(4-nitro-phenyl)deschloroepibatidine Is a Novel Potent Competitive Antagonist of Human Neuronal {alpha}4beta2 nAChRs Mol. Pharmacol., June 1, 2006; 69(6): 1945 - 1952. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Abdrakhmanova, L. Cleemann, J. Lindstrom, and M. Morad Differential Modulation of {beta}2 and {beta}4 Subunits of Human Neuronal Nicotinic Acetylcholine Receptors by Acidification Mol. Pharmacol., August 1, 2004; 66(2): 347 - 355. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Xiao and K. J. Kellar The Comparative Pharmacology and Up-Regulation of Rat Neuronal Nicotinic Receptor Subtype Binding Sites Stably Expressed in Transfected Mammalian Cells J. Pharmacol. Exp. Ther., July 1, 2004; 310(1): 98 - 107. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Moccia, C. Frost, R. Berra-Romani, F. Tanzi, and D. J. Adams Expression and function of neuronal nicotinic ACh receptors in rat microvascular endothelial cells Am J Physiol Heart Circ Physiol, February 1, 2004; 286(2): H486 - H491. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. W. Fitch, Y. Xiao, K. J. Kellar, and J. W. Daly Membrane potential fluorescence: A rapid and highly sensitive assay for nicotinic receptor channel function PNAS, April 15, 2003; 100(8): 4909 - 4914. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Sala, J. Mulet, S. Choi, S.-Y. Jung, S.-Y. Nah, H. Rhim, L. M. Valor, M. Criado, and S. Sala Effects of Ginsenoside Rg2 on Human Neuronal Nicotinic Acetylcholine Receptors J. Pharmacol. Exp. Ther., June 1, 2002; 301(3): 1052 - 1059. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Abdrakhmanova, J. Dorfman, Y. Xiao, and M. Morad Protons Enhance the Gating Kinetics of the alpha 3/beta 4 Neuronal Nicotinic Acetylcholine Receptor by Increasing Its Apparent Affinity to Agonists Mol. Pharmacol., February 1, 2002; 61(2): 369 - 378. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Meyer, Y. Xiao, and K. J. Kellar Agonist Regulation of Rat alpha 3beta 4 Nicotinic Acetylcholine Receptors Stably Expressed in Human Embryonic Kidney 293 Cells Mol. Pharmacol., September 1, 2001; 60(3): 568 - 576. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Giniatullin, E. M. Sokolova, S. Di Angelantonio, A. Skorinkin, M. V. Talantova, and A. Nistri Rapid Relief of Block by Mecamylamine of Neuronal Nicotinic Acetylcholine Receptors of Rat Chromaffin Cells In Vitro: An Electrophysiological and Modeling Study Mol. Pharmacol., October 1, 2000; 58(4): 778 - 787. [Abstract] [Full Text]
|
|
 |
 |
 |
|
 |
 |
 |
