JPET Assistant Professor of Medicine (Clinician-Educator)

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
 QUICK SEARCH:   [advanced]


     


This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Delbono, O.
Right arrow Articles by Sullivan, J. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Delbono, O.
Right arrow Articles by Sullivan, J. P.

Vol. 280, Issue 1, 428-438, 1997

Activation of the Recombinant Human alpha 7 Nicotinic Acetylcholine Receptor Significantly Raises Intracellular Free Calcium

O. Delbono1 , M. Gopalakrishnan, M. Renganathan, L. M. Monteggia, M. L. Messi and J. P. Sullivan

Departments of Physiology and Pharmacology (O.D., M.L.M.) and Internal Medicine (Gerontology) (O.D., M.R.), Bowman Gray School of Medicine of the Wake Forest University, Winston-Salem, North Carolina and Neuroscience Research (D-47W) (M.G., L.M.M., J.P.S.), Abbott Laboratories, Abbott Park, Illinois

The alpha 7 nicotinic acetylcholine receptor (nAChR) subtype, unlike other neuronal nicotinic receptors, exhibits a relatively high permeability to Ca++ ions. Although Ca++ entry through this receptor subtype has been implicated in various Ca++-dependent processes in the central nervous system, little is known about how this receptor modulates mammalian intracellular Ca++ dynamics. Intracellular Ca++ responses evoked by activation of the human alpha 7 nAChRs stably expressed in HEK-293 (human embryonic kidney) cells were studied. Inward current and intracellular Ca++ transients were recorded simultaneously in response to a fast drug application system. Current recordings under whole-cell voltage-clamp and fast ratiometric intracellular Ca++ imaging acquisition were synchronized to drug pulses. The mean peak [Ca++]i observed with 100 µM (-)-nicotine was 356 ± 48 nM (n = 8). The magnitude of the intracellular Ca++ elevation corresponds to a 20% fractional current carried by Ca++ ions. The EC50 of the intracellular Ca++ responses for (-)-nicotine, (±)-epibatidine, 1,1 dimethyl-4-phenyl-piperazinium and acetylcholine were 51, 3.5, 75 and 108 µM, respectively. These EC50 values strongly correlate with those recorded for the cationic inward current through alpha 7 nAChR. alpha -Bungarotoxin, methyllcaconitine or extracellular Ca++ chelation ablated (-)-nicotine-evoked increase in intracellular Ca++ concentration. This study provides evidence that cation influx through the human alpha 7 nAChR is sufficient to mediate a significant, transient, rise in intracellular Ca++ concentration.


Copyright © by The American Society for Pharmacology and Experimental Therapeutics



This article has been cited by other articles:


Home page
FASEB J.Home page
J. Arredondo, A. I. Chernyavsky, D. L. Jolkovsky, K. E. Pinkerton, and S. A. Grando
Receptor-mediated tobacco toxicity: acceleration of sequential expression of {alpha}5 and {alpha}7 nicotinic receptor subunits in oral keratinocytes exposed to cigarette smoke
FASEB J, May 1, 2008; 22(5): 1356 - 1368.
[Abstract] [Full Text] [PDF]


Home page
J. Neurophysiol.Home page
X. Guo and R. A. J. Lester
Ca2+ Flux and Signaling Implications by Nicotinic Acetylcholine Receptors in Rat Medial Habenula
J Neurophysiol, January 1, 2007; 97(1): 83 - 92.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Respir. Cell Mol. Bio.Home page
S. Razani-Boroujerdi and M. L. Sopori
Early Manifestations of NNK-Induced Lung Cancer: Role of Lung Immunity in Tumor Susceptibility
Am. J. Respir. Cell Mol. Biol., January 1, 2007; 36(1): 13 - 19.
[Abstract] [Full Text] [PDF]


Home page
FASEB J.Home page
J. Arredondo, A. I. Chernyavsky, D. L. Jolkovsky, K. E. Pinkerton, and S. A. Grando
Receptor-mediated tobacco toxicity: cooperation of the Ras/Raf-1/MEK1/ERK and JAK-2/STAT-3 pathways downstream of {alpha}7 nicotinic receptor in oral keratinocytes
FASEB J, October 1, 2006; 20(12): 2093 - 2101.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Pathol.Home page
J.-M. Tournier, K. Maouche, C. Coraux, J.-M. Zahm, I. Cloez-Tayarani, B. Nawrocki-Raby, A. Bonnomet, H. Burlet, F. Lebargy, M. Polette, et al.
{alpha}3{alpha}5{beta}2-Nicotinic Acetylcholine Receptor Contributes to the Wound Repair of the Respiratory Epithelium by Modulating Intracellular Calcium in Migrating Cells
Am. J. Pathol., January 1, 2006; 168(1): 55 - 68.
[Abstract] [Full Text] [PDF]


Home page
Biol. Reprod.Home page
C. Bray, J.-H. Son, P. Kumar, and S. Meizel
Mice Deficient in CHRNA7, a Subunit of the Nicotinic Acetylcholine Receptor, Produce Sperm with Impaired Motility
Biol Reprod, October 1, 2005; 73(4): 807 - 814.
[Abstract] [Full Text] [PDF]


Home page
J. Pharmacol. Exp. Ther.Home page
M. Diaz-Hernandez, J. Sanchez-Nogueiro, J. Pintor, and M. T. Miras-Portugal
Interaction between Dinucleotide and Nicotinic Receptors in Individual Cholinergic Terminals
J. Pharmacol. Exp. Ther., December 1, 2004; 311(3): 954 - 967.
[Abstract] [Full Text] [PDF]


Home page
Biol. Reprod.Home page
J.-H. Son and S. Meizel
Evidence Suggesting That the Mouse Sperm Acrosome Reaction Initiated by the Zona Pellucida Involves an {alpha}7 Nicotinic Acetylcholine Receptor
Biol Reprod, April 1, 2003; 68(4): 1348 - 1353.
[Abstract] [Full Text] [PDF]


Home page
Biol. Reprod.Home page
C. Bray, J.-H. Son, and S. Meizel
A Nicotinic Acetylcholine Receptor Is Involved in the Acrosome Reaction of Human Sperm Initiated by Recombinant Human ZP3
Biol Reprod, September 1, 2002; 67(3): 782 - 788.
[Abstract] [Full Text] [PDF]


Home page
Mol. Pharmacol.Home page
M. M. Francis, E. Y. Cheng, G. A. Weiland, and R. E. Oswald
Specific Activation of the alpha 7 Nicotinic Acetylcholine Receptor by a Quaternary Analog of Cocaine
Mol. Pharmacol., July 1, 2001; 60(1): 71 - 79.
[Abstract] [Full Text]


Home page
J. Cell Sci.Home page
V. Nguyen, A Ndoye, L. Hall, S Zia, J Arredondo, A. Chernyavsky, D. Kist, B. Zelickson, M. Lawry, and S. Grando
Programmed cell death of keratinocytes culminates in apoptotic secretion of a humectant upon secretagogue action of acetylcholine
J. Cell Sci., January 3, 2001; 114(6): 1189 - 1204.
[Abstract] [PDF]


Home page
J. Pharmacol. Exp. Ther.Home page
S. Zia, A. Ndoye, T. X. Lee, R. J. Webber, and S. A. Grando
Receptor-Mediated Inhibition of Keratinocyte Migration by Nicotine Involves Modulations of Calcium Influx and Intracellular Concentration
J. Pharmacol. Exp. Ther., June 1, 2000; 293(3): 973 - 981.
[Abstract] [Full Text]


Home page
J. Pharmacol. Exp. Ther.Home page
V. Gerzanich, F. Wang, A. Kuryatov, and J. Lindstrom
alpha 5 Subunit Alters Desensitization, Pharmacology, Ca++ Permeability and Ca++ Modulation of Human Neuronal alpha 3 Nicotinic Receptors
J. Pharmacol. Exp. Ther., July 1, 1998; 286(1): 311 - 320.
[Abstract] [Full Text]


Home page
J. Physiol.Home page
D. Ragozzino, B. Barabino, S. Fucile, and F. Eusebi
Ca2+ permeability of mouse and chick nicotinic acetylcholine receptors expressed in transiently transfected human cells
J. Physiol., March 15, 1998; 507(3): 749 - 757.
[Abstract] [Full Text] [PDF]


Home page
Mol. Pharmacol.Home page
R. M. Krause, B. Buisson, S. Bertrand, P.-J. Corringer, J.-L. Galzi, J.-P. Changeux, and D. Bertrand
Ivermectin: A Positive Allosteric Effector of the alpha 7 Neuronal Nicotinic Acetylcholine Receptor
Mol. Pharmacol., February 1, 1998; 53(2): 283 - 294.
[Abstract] [Full Text]


Home page
Proc. Natl. Acad. Sci. USAHome page
E. Palma, L. Maggi, F. Eusebi, and R. Miledi
Neuronal nicotinic threonine-for-leucine 247 alpha 7 mutant receptors show different gating kinetics when activated by acetylcholine or by the noncompetitive agonist 5-hydroxytryptamine
PNAS, September 2, 1997; 94(18): 9915 - 9919.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
S. Fucile, E. Palma, A. M. Mileo, R. Miledi, and F. Eusebi
Human neuronal threonine-for-leucine-248 alpha 7 mutant nicotinic acetylcholine receptors are highly Ca2+ permeable
PNAS, March 28, 2000; 97(7): 3643 - 3648.
[Abstract] [Full Text] [PDF]




Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
 Molecular Interventions Drug Metabolism and Disposition

Copyright © 1997 by the American Society for Pharmacology and Experimental Therapeutics.