 |
|||||
|
|||||
|
|||||
|
|||||
|
|||||
Previous Article | Next Article
The Journal of Neuroscience, March 1, 1999, 19(5):1691-1697
Inducible Genetic Suppression of Neuronal Excitability
David C. Johns1, Ruth Marx2, Richard E. Mains2, Brian O'Rourke1, and Eduardo Marbán1 1 Section of Molecular and Cellular Cardiology,
Division of Cardiology, and 2 Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205 Graded, reversible suppression of neuronal excitability represents a logical goal of therapy for epilepsy and intractable pain. To achieve such suppression, we have developed the means to transfer "electrical silencing" genes into neurons with sensitive control of transgene expression. An ecdysone-inducible promoter drives the expression of inwardly rectifying potassium channels in polycistronic adenoviral vectors. Infection of superior cervical ganglion neurons did not affect normal electrical activity but suppressed excitability after the induction of gene expression. These experiments demonstrate the feasibility of controlled ion channel expression after somatic gene transfer into neurons and serve as the prototype for a novel generalizable approach to modulate excitability.
Key words: genetic; neuronal excitability; viral gene transfer; inducible expression; gene therapy; adenovirus
Copyright © 1999 Society for Neuroscience 0270-6474/99/1951691-07$05.00/0
This article has been cited by other articles:
P. W. Howorth, S. R. Thornton, V. O'Brien, W. D. Smith, N. Nikiforova, A. G. Teschemacher, and A. E. Pickering
Retrograde Viral Vector-Mediated Inhibition of Pontospinal Noradrenergic Neurons Causes Hyperalgesia in Rats
J. Neurosci., October 14, 2009; 29(41): 12855 - 12864.
[Abstract] [Full Text] [PDF]
E. Lorenzetto, L. Caselli, G. Feng, W. Yuan, J. M. Nerbonne, J. R. Sanes, and M. Buffelli
Genetic perturbation of postsynaptic activity regulates synapse elimination in developing cerebellum
PNAS, September 22, 2009; 106(38): 16475 - 16480.
[Abstract] [Full Text] [PDF]
S. Kasparov and A. G. Teschemacher
The use of viral gene transfer in studies of brainstem noradrenergic and serotonergic neurons
Phil Trans R Soc B, September 12, 2009; 364(1529): 2565 - 2576.
[Abstract] [Full Text] [PDF]
X. Xu and H. M. Colecraft
Engineering Proteins for Custom Inhibition of CaV Channels
Physiology, August 1, 2009; 24(4): 210 - 218.
[Abstract] [Full Text] [PDF]
C.-L. Wang, L. Zhang, Y. Zhou, J. Zhou, X.-J. Yang, S.-m. Duan, Z.-Q. Xiong, and Y.-Q. Ding
Activity-Dependent Development of Callosal Projections in the Somatosensory Cortex
J. Neurosci., October 17, 2007; 27(42): 11334 - 11342.
[Abstract] [Full Text] [PDF]
D. L. Chao and G. J. Wang
Firing to Wire: A Role for Activity in Establishing Layer Specificity in the Cortex
J. Neurosci., October 10, 2007; 27(41): 10922 - 10923.
[Full Text] [PDF]
H. Duale, H. Waki, P. Howorth, S. Kasparov, A. G. Teschemacher, and J. F.R. Paton
Restraining influence of A2 neurons in chronic control of arterial pressure in spontaneously hypertensive rats
Cardiovasc Res, October 1, 2007; 76(1): 184 - 193.
[Abstract] [Full Text] [PDF]
J. R. Holt, E. A. Stauffer, D. Abraham, and G. S. G. Geleoc
Dominant-Negative Inhibition of M-Like Potassium Conductances in Hair Cells of the Mouse Inner Ear
J. Neurosci., August 15, 2007; 27(33): 8940 - 8951.
[Abstract] [Full Text] [PDF]
H. Mizuno, T. Hirano, and Y. Tagawa
Evidence for Activity-Dependent Cortical Wiring: Formation of Interhemispheric Connections in Neonatal Mouse Visual Cortex Requires Projection Neuron Activity
J. Neurosci., June 20, 2007; 27(25): 6760 - 6770.
[Abstract] [Full Text] [PDF]
H. Luan, W. C. Lemon, N. C. Peabody, J. B. Pohl, P. K. Zelensky, D. Wang, M. N. Nitabach, T. C. Holmes, and B. H. White
Functional Dissection of a Neuronal Network Required for Cuticle Tanning and Wing Expansion in Drosophila
J. Neurosci., January 11, 2006; 26(2): 573 - 584.
[Abstract] [Full Text] [PDF]
P. R. Le Tissier, D. F. Carmignac, S. Lilley, A. K. Sesay, C. J. Phelps, P. Houston, K. Mathers, C. Magoulas, D. Ogden, and I. C. A. F. Robinson
Hypothalamic Growth Hormone-Releasing Hormone (GHRH) Deficiency: Targeted Ablation of GHRH Neurons in Mice Using a Viral Ion Channel Transgene
Mol. Endocrinol., May 1, 2005; 19(5): 1251 - 1262.
[Abstract] [Full Text] [PDF]
S. Naik, C. K. Billington, R. M. Pascual, D. A. Deshpande, F. P. Stefano, T. A. Kohout, D. M. Eckman, J. L. Benovic, and R. B. Penn
Regulation of Cysteinyl Leukotriene Type 1 Receptor Internalization and Signaling
J. Biol. Chem., March 11, 2005; 280(10): 8722 - 8732.
[Abstract] [Full Text] [PDF]
M. Murata, E. Cingolani, A. D. McDonald, J. K. Donahue, and E. Marban
Creation of a Genetic Calcium Channel Blocker by Targeted Gem Gene Transfer in the Heart
Circ. Res., August 20, 2004; 95(4): 398 - 405.
[Abstract] [Full Text] [PDF]
E. S. Mohammadi, E. A. Ketner, D. C. Johns, and G. Ketner
Expression of the adenovirus E4 34k oncoprotein inhibits repair of double strand breaks in the cellular genome of a 293-based inducible cell line
Nucleic Acids Res., May 11, 2004; 32(8): 2652 - 2659.
[Abstract] [Full Text] [PDF]
H. S. Yoon and V. W. Yang
Requirement of Kruppel-like Factor 4 in Preventing Entry into Mitosis following DNA Damage
J. Biol. Chem., February 6, 2004; 279(6): 5035 - 5041.
[Abstract] [Full Text] [PDF]
B. F. Hinnebusch, A. Siddique, J. W. Henderson, M. S. Malo, W. Zhang, C. P. Athaide, M. A. Abedrapo, X. Chen, V. W. Yang, and R. A. Hodin
Enterocyte differentiation marker intestinal alkaline phosphatase is a target gene of the gut-enriched Kruppel-like factor
Am J Physiol Gastrointest Liver Physiol, January 1, 2004; 286(1): G23 - G30.
[Abstract] [Full Text] [PDF]
P. S. Lange, F. Er, N. Gassanov, and U. C. Hoppe
Andersen mutations of KCNJ2 suppress the native inward rectifier current IK1 in a dominant-negative fashion
Cardiovasc Res, August 1, 2003; 59(2): 321 - 327.
[Abstract] [Full Text] [PDF]
F. Er, R. Larbig, A. Ludwig, M. Biel, F. Hofmann, D. J. Beuckelmann, and U. C. Hoppe
Dominant-Negative Suppression of HCN Channels Markedly Reduces the Native Pacemaker Current If and Undermines Spontaneous Beating of Neonatal Cardiomyocytes
Circulation, January 28, 2003; 107(3): 485 - 489.
[Abstract] [Full Text] [PDF]
B. A. Alseikhan, C. D. DeMaria, H. M. Colecraft, and D. T. Yue
Engineered calmodulins reveal the unexpected eminence of Ca2+ channel inactivation in controlling heart excitation
PNAS, December 24, 2002; 99(26): 17185 - 17190.
[Abstract] [Full Text] [PDF]
E. M. Slimko, S. McKinney, D. J. Anderson, N. Davidson, and H. A. Lester
Selective Electrical Silencing of Mammalian Neurons In Vitro by the Use of Invertebrate Ligand-Gated Chloride Channels
J. Neurosci., September 1, 2002; 22(17): 7373 - 7379.
[Abstract] [Full Text] [PDF]
W. Guo, S. A. Malin, D. C. Johns, A. Jeromin, and J. M. Nerbonne
Modulation of Kv4-encoded K+ Currents in the Mammalian Myocardium by Neuronal Calcium Sensor-1
J. Biol. Chem., July 12, 2002; 277(29): 26436 - 26443.
[Abstract] [Full Text] [PDF]
H. Nadeau and H. A. Lester
NRSF Causes cAMP-Sensitive Suppression of Sodium Current in Cultured Hippocampal Neurons
J Neurophysiol, July 1, 2002; 88(1): 409 - 421.
[Abstract] [Full Text] [PDF]
H. A. E. Lechner, E. S. Lein, and E. M. Callaway
A Genetic Method for Selective and Quickly Reversible Silencing of Mammalian Neurons
J. Neurosci., July 1, 2002; 22(13): 5287 - 5290.
[Abstract] [Full Text] [PDF]
H. M Colecraft, B. Alseikhan, S. X Takahashi, D. Chaudhuri, S. Mittman, V. Yegnasubramanian, R. S Alvania, D. C Johns, E. Marban, and D. T Yue
Novel functional properties of Ca2+ channel {beta} subunits revealed by their expression in adult rat heart cells
J. Physiol., June 1, 2002; 541(2): 435 - 452.
[Abstract] [Full Text] [PDF]
S. Giovannardi, G. Forlani, M. Balestrini, E. Bossi, R. Tonini, E. Sturani, A. Peres, and R. Zippel
Modulation of the Inward Rectifier Potassium Channel IRK1 by the Ras Signaling Pathway
J. Biol. Chem., March 29, 2002; 277(14): 12158 - 12163.
[Abstract] [Full Text] [PDF]
C. J. McCormick, D. J. Rowlands, and M. Harris
Efficient delivery and regulable expression of hepatitis C virus full-length and minigenome constructs in hepatocyte-derived cell lines using baculovirus vectors
J. Gen. Virol., February 1, 2002; 83(2): 383 - 394.
[Abstract] [Full Text] [PDF]
Q. Cheng, P. M. Burkat, J. C. Kulli, and J. Yang
GABACrho 1 Subunits Form Functional Receptors But Not Functional Synapses in Hippocampal Neurons
J Neurophysiol, November 1, 2001; 86(5): 2605 - 2615.
[Abstract] [Full Text] [PDF]
C. B. Chan, D. De Leo, J. W. Joseph, T. S. McQuaid, X. F. Ha, F. Xu, R. G. Tsushima, P. S. Pennefather, A. M. F. Salapatek, and M. B. Wheeler
Increased Uncoupling Protein-2 Levels in {beta}-cells Are Associated With Impaired Glucose-Stimulated Insulin Secretion: Mechanism of Action
Diabetes, June 1, 2001; 50(6): 1302 - 1310.
[Abstract] [Full Text]
Q. Cheng, J. C. Kulli, and J. Yang
Suppression of Neuronal Hyperexcitability and Associated Delayed Neuronal Death by Adenoviral Expression of GABAC Receptors
J. Neurosci., May 15, 2001; 21(10): 3419 - 3428.
[Abstract] [Full Text] [PDF]
R. A Li, J. Miake, U. C Hoppe, D. C Johns, E. Marban, and H B. Nuss
Functional consequences of the arrhythmogenic G306R KvLQT1 K+ channel mutant probed by viral gene transfer in cardiomyocytes
J. Physiol., May 15, 2001; 533(1): 127 - 133.
[Abstract] [Full Text] [PDF]
U. C. Hoppe, E. Marban, and D. C. Johns
Distinct gene-specific mechanisms of arrhythmia revealed by cardiac gene transfer of two long QT disease genes, HERG and KCNE1
PNAS, April 24, 2001; 98(9): 5335 - 5340.
[Abstract] [Full Text] [PDF]
R. A. Baines, J. P. Uhler, A. Thompson, S. T. Sweeney, and M. Bate
Altered Electrical Properties in Drosophila Neurons Developing without Synaptic Transmission
J. Neurosci., March 1, 2001; 21(5): 1523 - 1531.
[Abstract] [Full Text] [PDF]
R. El Meskini, L. Jin, R. Marx, A. Bruzzaniti, J. Lee, R. B. Emeson, and R. E. Mains
A Signal Sequence Is Sufficient for Green Fluorescent Protein to Be Routed to Regulated Secretory Granules
Endocrinology, February 1, 2001; 142(2): 864 - 873.
[Abstract] [Full Text] [PDF]
C.-C. Shieh, M. Coghlan, J. P. Sullivan, and M. Gopalakrishnan
Potassium Channels: Molecular Defects, Diseases, and Therapeutic Opportunities
Pharmacol. Rev., December 1, 2000; 52(4): 557 - 594.
[Abstract] [Full Text] [PDF]
H. Nadeau, S. McKinney, D. J. Anderson, and H. A. Lester
ROMK1 (Kir1.1) Causes Apoptosis and Chronic Silencing of Hippocampal Neurons
J Neurophysiol, August 1, 2000; 84(2): 1062 - 1075.
[Abstract] [Full Text] [PDF]
M. A. Otieno and T. W. Kensler
A Role for Protein Kinase C-{{delta}} in the Regulation of Ornithine Decarboxylase Expression by Oxidative Stress
Cancer Res., August 1, 2000; 60(16): 4391 - 4396.
[Abstract] [Full Text]
M. T. Perez-Garcia, J. R. Lopez-Lopez, A. M. Riesco, U. C. Hoppe, E. Marban, C. Gonzalez, and D. C. Johns
Viral Gene Transfer of Dominant-Negative Kv4 Construct Suppresses an O2-Sensitive K+ Current in Chemoreceptor Cells
J. Neurosci., August 1, 2000; 20(15): 5689 - 5695.
[Abstract] [Full Text] [PDF]
M. Sasaki, M. Gonzalez-Zulueta, H. Huang, W. J. Herring, S. Ahn, D. D. Ginty, V. L. Dawson, and T. M. Dawson
Dynamic regulation of neuronal NO synthase transcription by calcium influx through a CREB family transcription factor-dependent mechanism
PNAS, July 18, 2000; 97(15): 8617 - 8622.
[Abstract] [Full Text] [PDF]
J. Seharaseyon, N. Sasaki, A. Ohler, T. Sato, H. Fraser, D. C. Johns, B. O'Rourke, and E. Marban
Evidence against Functional Heteromultimerization of the KATP Channel Subunits Kir6.1 and Kir6.2
J. Biol. Chem., June 2, 2000; 275(23): 17561 - 17565.
[Abstract] [Full Text] [PDF]
E. Marban
Gene Therapy for Common Acquired Diseases of the Heart : The Sirens’ Song
Circulation, April 4, 2000; 101(13): 1498 - 1499.
[Full Text] [PDF]
Z.-Q. Xiong and J. L. Stringer
Cesium Induces Spontaneous Epileptiform Activity Without Changing Extracellular Potassium Regulation in Rat Hippocampus
J Neurophysiol, December 1, 1999; 82(6): 3339 - 3346.
[Abstract] [Full Text] [PDF]
R. Marx, R. El Meskini, D. C. Johns, and R. E. Mains
Differences in the Ways Sympathetic Neurons and Endocrine Cells Process, Store, and Secrete Exogenous Neuropeptides and Peptide-Processing Enzymes
J. Neurosci., October 1, 1999; 19(19): 8300 - 8311.
[Abstract] [Full Text] [PDF]
H. Hu, T. Sato, J. Seharaseyon, Y. Liu, D. C. Johns, B. O'Rourke, and E. Marbán
Pharmacological and Histochemical Distinctions Between Molecularly Defined Sarcolemmal KATP Channels and Native Cardiac Mitochondrial KATP Channels
Mol. Pharmacol., June 1, 1999; 55(6): 1000 - 1005.
[Abstract] [Full Text]
X. Chen, D. C. Johns, D. E. Geiman, E. Marban, D. T. Dang, G. Hamlin, R. Sun, and V. W. Yang
Kruppel-like Factor 4 (Gut-enriched Kruppel-like Factor) Inhibits Cell Proliferation by Blocking G1/S Progression of the Cell Cycle
J. Biol. Chem., August 3, 2001; 276(32): 30423 - 30428.
[Abstract] [Full Text] [PDF]
W. Lee-Kwon, D. C. Johns, B. Cha, M. Cavet, J. Park, P. Tsichlis, and M. Donowitz
Constitutively Active Phosphatidylinositol 3-Kinase and AKT Are Sufficient to Stimulate the Epithelial Na+/H+ Exchanger 3
J. Biol. Chem., August 10, 2001; 276(33): 31296 - 31304.
[Abstract] [Full Text] [PDF]
E. Saez, M. C. Nelson, B. Eshelman, E. Banayo, A. Koder, G. J. Cho, and R. M. Evans
Identification of ligands and coligands for the ecdysone-regulated gene switch
PNAS, December 19, 2000; 97(26): 14512 - 14517.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|