Neurosteroids that can enhance GABAA receptor sensitivity protect cerebellar Purkinje cells against transient episodes of global brain ischemia, but little is known about how ischemia affects GABAergic transmission onto Purkinje cells. Here we use patch-clamp recording from Purkinje cells in acutely prepared slices of rat cerebellum to determine how ischemia affects GABAergic signaling to Purkinje cells. In voltage-clamped Purkinje cells, exposing slices to solutions designed to simulate brain ischemia caused an early, partial suppression of the frequency of spontaneous inhibitory post synaptic currents (sIPSCs), but after 5-8 min GABA accumulated in the extracellular space around Purkinje cells, generating a large (~17 nS), sustained GABAA receptor-mediated conductance. The sustained GABAA conductance occurred in parallel with an even larger (~117 nS) glutamate receptor-mediated conductance, but blocking GABAA receptors did not affect the timing or magnitude of the glutamate conductance, and blocking glutamate receptors did not affect the timing or magnitude of the GABAA conductance. Despite the lack of interaction between GABA and glutamate, blocking GABAA receptors significantly accelerated the onset of the Purkinje cell "ischemic" depolarization (ID), as assessed with current-clamp recordings from Purkinje cells or field potential recordings in the dendritic field of the Purkinje cells. The Purkinje cell ID occurred ~2 min prior to the sustained glutamate release under control conditions and a further 1-2 min earlier when GABAA receptors were blocked. Tissue swelling, as assessed by monitoring light transmittance through the slice, peaked just after the ID, prior to the sustained glutamate release, but was not affected by blocking GABAA receptors. These data indicate that ischemia induces the Purkinje cell ID and tissue swelling prior to the sustained glutamate release, and that blocking GABAA receptors accelerates the onset of the ID without affecting tissue swelling. Taken together these data may explain why Purkinje cells are one of the most ischemia sensitive neurons in the brain despite lacking NMDA receptors, and why neurosteroids that enhance GABAA receptor function protect Purkinje cells against transient episodes of global brain ischemia.
|Original language||English (US)|
|Number of pages||10|
|State||Published - Jun 1 2010|
- Purkinje cell
- Synaptic transmission
ASJC Scopus subject areas