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 Alden, K. J.
Right arrow Articles by García, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Alden, K. J.
Right arrow Articles by García, J.

Vol. 297, Issue 2, 727-735, May 2001

Differential Effect of Gabapentin on Neuronal and Muscle Calcium Currents

Kris J. Alden and Jesús García

Department of Physiology & Biophysics, University of Illinois at Chicago College of Medicine, Chicago, Illinois

Calcium channels modulate cell function by controlling Ca2+ influx. A main component of these proteins is the alpha 2/delta subunit. Nevertheless, how this subunit regulates channel activity in situ is unclear. Gabapentin (GBP), an analgesic and anti-epileptic agent with an unknown mechanism of action, specifically binds to the alpha 2/delta subunit. Using the patch clamp technique, we tested the effects of GBP on Ca2+ currents from dorsal root ganglion (DRG) cells, the mediators of pain perception, to determine how GBP binding modifies channel activity. In DRGs, GBP significantly reduced whole cell Ca2+ current amplitude at positive membrane potentials when a pulse preceded the test pulses or when cells were stimulated with a train of pulses. In control cells, neither prepulse depolarization nor pulse trains reduced Ca2+ currents at positive potentials. GBP did not reduce the low-voltage activated Ca2+ current under any experimental condition. Similar to DRG cells, GBP attenuated Ca2+ current in skeletal myotubes at positive membrane potentials in the presence of a depolarizing prepulse. However, GBP did not significantly alter Ca2+ currents in cardiac myocytes. Reverse transcription-polymerase chain reaction was used to confirm expression of the alpha 2/delta subunit in these cells. Each cell type expressed multiple isoforms of alpha 2/delta . Muscle cells showed a more variable expression of alpha 2/delta subunits than did DRG cells. Our results suggest a possible participation of the alpha 2/delta subunit in the action of GBP. Our data also indicate that GBP inhibits Ca2+ channels in a use- and voltage-dependent manner at a therapeutically relevant concentration.

0022-3565/01/2972-0727$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2001 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Anesth. Analg.Home page
S. Koc, D. Memis, and N. Sut
The Preoperative Use of Gabapentin, Dexamethasone, and Their Combination in Varicocele Surgery: A Randomized Controlled Trial
Anesth. Analg., October 1, 2007; 105(4): 1137 - 1142.
[Abstract] [Full Text] [PDF]

Home page
 The Annals of PharmacotherapyHome page
M. Tuccori, G. Lombardo, F. Lapi, A. Vannacci, C. Blandizzi, and M. Del Tacca
Gabapentin-Induced Severe Myopathy
Ann. Pharmacother., July 1, 2007; 41(7): 1301 - 1305.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
K. D. Micheva, C. P. Taylor, and S. J Smith
Pregabalin Reduces the Release of Synaptic Vesicles from Cultured Hippocampal Neurons
Mol. Pharmacol., August 1, 2006; 70(2): 467 - 476.
[Abstract] [Full Text] [PDF]

Home page
 Ann Rheum DisHome page
C Boileau, J Martel-Pelletier, J Brunet, D Schrier, C Flory, M Boily, and J-P Pelletier
PD-0200347, an {alpha}2{delta} ligand of the voltage gated calcium channel, inhibits in vivo activation of the Erk1/2 pathway in osteoarthritic chondrocytes: a PKC{alpha} dependent effect
Ann Rheum Dis, May 1, 2006; 65(5): 573 - 580.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
S. Remy and H. Beck
Molecular and cellular mechanisms of pharmacoresistance in epilepsy
Brain, January 1, 2006; 129(1): 18 - 35.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
K. D. Garcia, T. Shah, and J. Garcia
Immunolocalization of type 2 inositol 1,4,5-trisphosphate receptors in cardiac myocytes from newborn mice
Am J Physiol Cell Physiol, October 1, 2004; 287(4): C1048 - C1057.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
K. J. Alden and J. Garcia
Dissociation of charge movement from calcium release and calcium current in skeletal myotubes by gabapentin
Am J Physiol Cell Physiol, September 1, 2002; 283(3): C941 - C949.
[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 © 2001 by the American Society for Pharmacology and Experimental Therapeutics.