![[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}
|
|
|
|
|
||
Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York
We determined the effect of flufenamic acid (FFA) and related derivatives
on gap junction channel currents, applying the dual whole-cell patch-clamp
technique to pairs of N2A neuroblastoma cells transfected with various
connexins. FFA reduced gap junction channel currents in a reversible and
concentration-dependent manner. Half-maximal concentrations for FFA-induced
reduction of junctional conductance in cell pairs coupled by different
connexins were similar (20 to 60 µM), indicating that FFA does not greatly
discriminate between connexin subtypes. Hill coefficients for blockade were
approximately 3, indicating a high degree of cooperativity. Analogs of FFA
also reduced junctional conductance with similar potencies, whereas other
unrelated chloride channel blockers had no effect. Inhibition of gap junction
channels by FFA (pKa 
3.8) was increased at low
external pH, suggesting that the uncharged form of the drug is important for
blockade. The effect of FFA did not seem to be mediated by direct binding of
the drug to the pore of the gap junction channel. Internal application of high
concentrations of FFA by addition to patch pipettes did not cause inhibition
of channel currents. The magnitude of inhibition was neither voltage-dependent
nor influenced by the nature of permeant ion. Single-channel recordings
indicated that FFA reduced the channel-open probability without modifying the
current amplitude and induced slow transitions between open and closed states.
We propose that FFA inhibits gap junctions by inducing a conformational change
in the protein upon binding to a site that is presumably located within the
membrane.
Address correspondence to: Dr. Miduturu Srinivas, Department of Neuroscience, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461. E-mail: msriniva{at}aecom.yu.edu
This article has been cited by other articles:
|
|
 |
|
  C. M. L. Hutnik, C. E. Pocrnich, H. Liu, D. W. Laird, and Q. Shao The Protective Effect of Functional Connexin43 Channels on a Human Epithelial Cell Line Exposed to Oxidative Stress Invest. Ophthalmol. Vis. Sci., February 1, 2008; 49(2): 800 - 806. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Crowder, M. S. Saha, R. W. Pace, H. Zhang, G. D. Prestwich, and C. A. Del Negro Phosphatidylinositol 4,5-bisphosphate regulates inspiratory burst activity in the neonatal mouse preBotzinger complex J. Physiol., August 1, 2007; 582(3): 1047 - 1058. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Bai, C. del Corsso, M. Srinivas, and D. C. Spray Block of Specific Gap Junction Channel Subtypes by 2-Aminoethoxydiphenyl Borate (2-APB) J. Pharmacol. Exp. Ther., December 1, 2006; 319(3): 1452 - 1458. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Reigada, W. Lu, and C. H. Mitchell Glutamate acts at NMDA receptors on fresh bovine and on cultured human retinal pigment epithelial cells to trigger release of ATP J. Physiol., September 15, 2006; 575(3): 707 - 720. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. P. Schools, M. Zhou, and H. K. Kimelberg Development of Gap Junctions in Hippocampal Astrocytes: Evidence That Whole Cell Electrophysiological Phenotype Is an Intrinsic Property of the Individual Cell J Neurophysiol, September 1, 2006; 96(3): 1383 - 1392. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. T. Barbe, H. Monyer, and R. Bruzzone Cell-Cell Communication Beyond Connexins: The Pannexin Channels Physiology, April 1, 2006; 21(2): 103 - 114. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. K. Tryba, F. Pena, and J.-M. Ramirez Gasping activity in vitro: a rhythm dependent on 5-HT2A receptors. J. Neurosci., March 8, 2006; 26(10): 2623 - 2634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. O. Suadicani, C. F. Brosnan, and E. Scemes P2X7 Receptors Mediate ATP Release and Amplification of Astrocytic Intercellular Ca2+ Signaling J. Neurosci., February 1, 2006; 26(5): 1378 - 1385. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Lyall, H. Pasley, T.-H. T. Phan, S. Mummalaneni, G. L. Heck, A. K. Vinnikova, and J. A. DeSimone Intracellular pH Modulates Taste Receptor Cell Volume and the Phasic Part of the Chorda Tympani Response to Acids J. Gen. Physiol., December 27, 2005; 127(1): 15 - 34. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Zhang, W. Tang, S. Ahmad, J. A. Sipp, P. Chen, and X. Lin Gap junction-mediated intercellular biochemical coupling in cochlear supporting cells is required for normal cochlear functions PNAS, October 18, 2005; 102(42): 15201 - 15206. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T.-Y. Huang and M. Hanani Morphological and electrophysiological changes in mouse dorsal root ganglia after partial colonic obstruction Am J Physiol Gastrointest Liver Physiol, October 1, 2005; 289(4): G670 - G678. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Del Negro, C. Morgado-Valle, J. A. Hayes, D. D. Mackay, R. W. Pace, E. A. Crowder, and J. L. Feldman Sodium and Calcium Current-Mediated Pacemaker Neurons and Respiratory Rhythm Generation J. Neurosci., January 12, 2005; 25(2): 446 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. E. Farris, C. L. LeBlanc, J. Goswami, and A. J. Ricci Probing the pore of the auditory hair cell mechanotransducer channel in turtle J. Physiol., August 1, 2004; 558(3): 769 - 792. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. P Moreno Biophysical properties of homomeric and heteromultimeric channels formed by cardiac connexins Cardiovasc Res, May 1, 2004; 62(2): 276 - 286. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
