| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
1. Current mediated by GABAA receptors was examined in pyramidal cells acutely dissociated from the hippocampus of mature guinea-pigs. Current responses were measured using whole-cell voltage-clamp recordings. An internal perfusion technique was used to change the intracellular contents during recording. 2. Application of GABA (100-300 microM) by short duration pressure pulses produced outward current responses at a holding potential of -10 mV. When recordings were made with intracellular solutions which did not contain Mg-ATP, GABA responses progressively decreased to less than 10% of their initial values after 10 min. This 'run-down' of the GABA response could not be accounted for by desensitization since the rate of run-down was not dependent upon agonist application. 3. The run-down of the GABAA response was reversed when Mg2+ (4 mM) and ATP (2 mM) were introduced into the intracellular perfusate. In addition to the presence of Mg-ATP, buffering of Ca2+ in the intracellular solution to low levels (approximately 10(-8) M) was also necessary to stabilize the GABAA response. 4. The role of a phosphorylation process in regulating the GABAA receptor was tested. After the GABA response stabilized, introduction of alkaline phosphatase (100 micrograms/ml) to the intracellular perfusate caused a complete run-down of the GABA response. 5. Stable GABA responses were obtained when ATP was replaced by ATP-gamma-S (adenosine 5'-O-(thiotriphosphate), an analogue of ATP that donates a thiophosphate group resulting in a product that is more resistant to hydrolysis. Following such treatment GABA responses declined more slowly after the introduction of intracellular alkaline phosphatase. 6. Run-down of GABA responses accelerated when intracellular Ca2+ concentration ([Ca2+]i) was elevated to about 5 x 10(-4) M. The run-down caused by elevated [Ca2+]i could be stopped and reversed by reducing [Ca2+]i to about 10(-8) M. 7. The introduction of ATP-gamma-S to the intracellular medium retarded the run-down of GABA responses caused by elevation of [Ca2+]i. 8. N-(6-Aminohexyl)-5-chloro-1-naphthalenesulphonamide (W-7), a calmodulin inhibitor, reduced the rate of run-down induced by elevated [Ca2+]i. 9. These results suggest that the function of the GABAA receptor is maintained by phosphorylation of the receptor or some closely associated regulatory molecule. Elevation of [Ca2+]i destabilizes the function of the GABAA receptor, probably by activating a Ca2+/calmodulin-dependent phosphatase.
This article has been cited by other articles:
|
|
 |
|
  J. J. Laschet, I. Kurcewicz, F. Minier, S. Trottier, J. Khallou-Laschet, J. Louvel, S. Gigout, B. Turak, A. Biraben, J.-M. Scarabin, et al. Dysfunction of GABAA receptor glycolysis-dependent modulation in human partial epilepsy PNAS, February 27, 2007; 104(9): 3472 - 3477. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Yang, L. S. Benardo, H. Valsamis, and D. S. F. Ling Acute Injury to Superficial Cortex Leads to a Decrease in Synaptic Inhibition and Increase in Excitation in Neocortical Layer V Pyramidal Cells J Neurophysiol, January 1, 2007; 97(1): 178 - 187. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Kantrowitz, N. N. Francis, A. Salah, and K. L. Perkins Synaptic Depolarizing GABA Response in Adults Is Excitatory and Proconvulsive When GABAB Receptors Are Blocked J Neurophysiol, May 1, 2005; 93(5): 2656 - 2667. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. J Allen and D. Attwell The effect of simulated ischaemia on spontaneous GABA release in area CA1 of the juvenile rat hippocampus J. Physiol., December 1, 2004; 561(2): 485 - 498. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Laschet, F. Minier, I. Kurcewicz, M. H. Bureau, S. Trottier, F. Jeanneteau, N. Griffon, B. Samyn, J. Van Beeumen, J. Louvel, et al. Glyceraldehyde-3-Phosphate Dehydrogenase Is a GABAA Receptor Kinase Linking Glycolysis to Neuronal Inhibition J. Neurosci., September 1, 2004; 24(35): 7614 - 7622. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Hinkle and R. L. Macdonald {beta} Subunit Phosphorylation Selectively Increases Fast Desensitization and Prolongs Deactivation of {alpha}1{beta}1{gamma}2L and {alpha}1{beta}3{gamma}2L GABAA Receptor Currents J. Neurosci., December 17, 2003; 23(37): 11698 - 11710. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Mizoguchi, T. Kanematsu, M. Hirata, and J. Nabekura A Rapid Increase in the Total Number of Cell Surface Functional GABAA Receptors Induced by Brain-derived Neurotrophic Factor in Rat Visual Cortex J. Biol. Chem., November 7, 2003; 278(45): 44097 - 44102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. H. Chang, V. C. Kotak, and D. H. Sanes Long-Term Depression of Synaptic Inhibition Is Expressed Postsynaptically in the Developing Auditory System J Neurophysiol, September 1, 2003; 90(3): 1479 - 1488. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Alix, F. Grolleau, and B. Hue Ca2+/Calmodulin-Dependent Protein Kinase Regulates GABA-Activated Cl- Current in Cockroach Dorsal Unpaired Median Neurons J Neurophysiol, June 1, 2002; 87(6): 2972 - 2982. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Centonze, E. Saulle, A. Pisani, G. Bernardi, and P. Calabresi Adenosine-mediated inhibition of striatal GABAergic synaptic transmission during in vitro ischaemia Brain, September 1, 2001; 124(9): 1855 - 1865. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. D. Fraser, D. Doll, and B. A. MacVicar Serine/Threonine Protein Phosphatases and Synaptic Inhibition Regulate the Expression of Cholinergic-Dependent Plateau Potentials J Neurophysiol, March 1, 2001; 85(3): 1197 - 1205. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. K. Meyer, C. Olenik, F. Hofmann, H. Barth, J. Leemhuis, I. Brunig, K. Aktories, and W. Norenberg Regulation of Somatodendritic GABAA Receptor Channels in Rat Hippocampal Neurons: Evidence for a Role of the Small GTPase Rac1 J. Neurosci., September 15, 2000; 20(18): 6743 - 6751. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Shew, S. Yip, and B. R. Sastry Mechanisms Involved in Tetanus-Induced Potentiation of Fast IPSCs in Rat Hippocampal CA1 Neurons J Neurophysiol, June 1, 2000; 83(6): 3388 - 3401. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. C. Solomon, N. H. Edelman, and J. A. Neubauer Pre-Botzinger Complex Functions as a Central Hypoxia Chemosensor for Respiration In Vivo J Neurophysiol, May 1, 2000; 83(5): 2854 - 2868. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. I. Banks and R. A. Pearce Kinetic Differences between Synaptic and Extrasynaptic GABAA Receptors in CA1 Pyramidal Cells J. Neurosci., February 1, 2000; 20(3): 937 - 948. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Chery and Y. De Koninck Junctional versus Extrajunctional Glycine and GABAA Receptor-Mediated IPSCs in Identified Lamina I Neurons of the Adult Rat Spinal Cord J. Neurosci., September 1, 1999; 19(17): 7342 - 7355. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kapur, K. F. Haas, and R. L. Macdonald Physiological Properties of GABAA Receptors From Acutely Dissociated Rat Dentate Granule Cells J Neurophysiol, May 1, 1999; 81(5): 2464 - 2471. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Poisbeau, M. C. Cheney, M. D. Browning, and I. Mody Modulation of Synaptic GABAA Receptor Function by PKA and PKC in Adult Hippocampal Neurons J. Neurosci., January 15, 1999; 19(2): 674 - 683. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sciancalepore, J. Gyori, and E. Cherubini Facilitation of Miniature GABAergic Currents by Ruthenium Red in Neonatal Rat Hippocampal Neurons J Neurophysiol, November 1, 1998; 80(5): 2316 - 2322. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Akopian, R. Gabriel, and P. Witkovsky Calcium Released From Intracellular Stores Inhibits GABAA-Mediated Currents in Ganglion Cells of the Turtle Retina J Neurophysiol, September 1, 1998; 80(3): 1105 - 1115. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. J. Luhmann, N. Karpuk, M. Qu, and K. Zilles Characterization of Neuronal Migration Disorders in Neocortical Structures. II. Intracellular In Vitro Recordings J Neurophysiol, July 1, 1998; 80(1): 92 - 102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. L. Gaspary, W. Wang, and G. B. Richerson Carrier-Mediated GABA Release Activates GABA Receptors on Hippocampal Neurons J Neurophysiol, July 1, 1998; 80(1): 270 - 281. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R.-Q. Huang and G. H. Dillon Maintenance of Recombinant Type A gamma -Aminobutyric Acid Receptor Function: Role of Protein Tyrosine Phosphorylation and Calcineurin J. Pharmacol. Exp. Ther., July 1, 1998; 286(1): 243 - 255. [Abstract] [Full Text]
|
|
|
|
|
|
F.E.N. L. Beau and B. E. Alger Transient Suppression of GABAA-Receptor-Mediated IPSPs After Epileptiform Burst Discharges in CA1 Pyramidal Cells J Neurophysiol, February 1, 1998; 79(2): 659 - 669. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. X. Chen, K. L. Perkins, and R. K. S. Wong Zn2+ Blocks the NMDA- and Ca2+-Triggered Postexposure Current Ipe in Hippocampal Pyramidal Cells J Neurophysiol, February 1, 1998; 79(2): 1124 - 1126. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. D. Bennett, J. R. Huguenard, and D. A. Prince Adrenoceptor-Mediated Elevation of Ambient GABA Levels Activates Presynaptic GABAB Receptors in Rat Sensorimotor Cortex J Neurophysiol, July 1, 1997; 78(1): 561 - 566. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Wan, H. Y. Man, J. Braunton, W. Wang, M. W. Salter, L. Becker, and Y. T. Wang Modulation of GABAA Receptor Function by Tyrosine Phosphorylation of beta Subunits J. Neurosci., July 1, 1997; 17(13): 5062 - 5069. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Obrietan and A. N. van den Pol GABA Activity Mediating Cytosolic Ca2+ Rises in Developing Neurons Is Modulated by cAMP-Dependent Signal Transduction J. Neurosci., June 15, 1997; 17(12): 4785 - 4799. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. X. Chen, K. L. Perkins, D. W. Choi, and R. K. S. Wong Secondary Activation of a Cation Conductance Is Responsible for NMDA Toxicity in Acutely Isolated Hippocampal Neurons J. Neurosci., June 1, 1997; 17(11): 4032 - 4036. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Koplas, R. L. Rosenberg, and G. S. Oxford The Role of Calcium in the Desensitization of Capsaicin Responses in Rat Dorsal Root Ganglion Neurons J. Neurosci., May 15, 1997; 17(10): 3525 - 3537. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. Bureau and J. J. Laschet Endogenous Phosphorylation of Distinct [IMAGE]-Aminobutyric Acid Type A Receptor Polypeptides by Ser/Thr and Tyr Kinase Activities Associated with the Purified Receptor J. Biol. Chem., November 3, 1995; 270(44): 26482 - 26487. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
