Inducible genetic suppression of neuronal excitability

Graded, reversible suppression of neuronal excitability represents a logica l goal of therapy for epilepsy and intractable pain. To achieve such suppre ssion, we have developed the means to transfer "electrical silencing" genes into neurons with sensitive control of transgene expression. An ecdysone-i nducible promoter drives the expression of inwardly rectifying potassium ch annels in polycistronic adenoviral vectors. Infection of superior cervical ganglion neurons did not affect normal electrical activity but suppressed e xcitability after the induction of gene expression. These experiments demon strate the feasibility of controlled ion channel expression after somatic g ene transfer into neurons and serve as the prototype for a novel generaliza ble approach to modulate excitability.