Activation of the GABA(A)-receptor delta-subunit gene promoter following pentylenetetrazole-induced seizures in transgenic mice.

An impairment of GABA(A)-receptor-mediated inhibitory neurotransmission has been implicated in the development of epileptic seizures. To determine whether seizures affect GABA(A)-receptor gene transcription in vivo, a transgenic mouse line carrying a lacZ-fusion gene driven by GABA(A)-receptor delta-subunit promoter and upstream sequences was subjected to pentylenetetrazol (PTZ)-induced seizures. After injection of a single convulsive dose of PTZ, the activity of the delta-subunit promoter, as monitored by beta-galactosidase immunohistochemistry, was increased selectively in neurons of layers II-IV of neocortex. In contrast, mice kindled by repeated administration of initially subconvulsive doses of PTZ did not show a change in transgene expression, even shortly after the last PTZ-induced seizure. These results show that transient changes in transcription of the GABA(A)-receptor delta-subunit gene occur after acute seizures, but not after kindling. The limited responsiveness of the GABA(A)-receptor delta-subunit promoter after repeated stimulation may reflect an inappropriate adaptation of cellular responses to recurrent excitation, thereby contributing to the development of seizure disorders.