Inducible genetic suppression of neuronal excitability

David C. Johns, Ruth Marx-Rattner, Richard E. Mains, Brian O'Rourke, Eduardo Marbán

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1691-1697
Number of pages7
JournalJournal of Neuroscience
Volume19
Issue number5
StatePublished - Mar 1 1999

Fingerprint

Genetic Suppression
Neurons
Inwardly Rectifying Potassium Channel
Ecdysone
Intractable Pain
Superior Cervical Ganglion
Gene Silencing
Transgenes
Ion Channels
Epilepsy
Gene Expression
Infection
Genes
Therapeutics

Keywords

  • Adenovirus
  • Gene therapy
  • Genetic
  • Inducible expression
  • Neuronal excitability
  • Vital gene transfer

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Inducible genetic suppression of neuronal excitability. / Johns, David C.; Marx-Rattner, Ruth; Mains, Richard E.; O'Rourke, Brian; Marbán, Eduardo.

In: Journal of Neuroscience, Vol. 19, No. 5, 01.03.1999, p. 1691-1697.

Research output: Contribution to journalArticle

Johns, DC, Marx-Rattner, R, Mains, RE, O'Rourke, B & Marbán, E 1999, 'Inducible genetic suppression of neuronal excitability', Journal of Neuroscience, vol. 19, no. 5, pp. 1691-1697.
Johns, David C. ; Marx-Rattner, Ruth ; Mains, Richard E. ; O'Rourke, Brian ; Marbán, Eduardo. / Inducible genetic suppression of neuronal excitability. In: Journal of Neuroscience. 1999 ; Vol. 19, No. 5. pp. 1691-1697.
@article{63dc8c9f1f7049098bc07bd239c166ef,
title = "Inducible genetic suppression of neuronal excitability",
abstract = "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.",
keywords = "Adenovirus, Gene therapy, Genetic, Inducible expression, Neuronal excitability, Vital gene transfer",
author = "Johns, {David C.} and Ruth Marx-Rattner and Mains, {Richard E.} and Brian O'Rourke and Eduardo Marb{\'a}n",
year = "1999",
month = "3",
day = "1",
language = "English (US)",
volume = "19",
pages = "1691--1697",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "5",

}

TY - JOUR

T1 - Inducible genetic suppression of neuronal excitability

AU - Johns, David C.

AU - Marx-Rattner, Ruth

AU - Mains, Richard E.

AU - O'Rourke, Brian

AU - Marbán, Eduardo

PY - 1999/3/1

Y1 - 1999/3/1

N2 - 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.

AB - 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.

KW - Adenovirus

KW - Gene therapy

KW - Genetic

KW - Inducible expression

KW - Neuronal excitability

KW - Vital gene transfer

UR - http://www.scopus.com/inward/record.url?scp=0033103345&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033103345&partnerID=8YFLogxK

M3 - Article

C2 - 10024355

AN - SCOPUS:0033103345

VL - 19

SP - 1691

EP - 1697

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 5

ER -