Role of Na-K pump potassium regulation and IPSPs in seizures and spreading depression in immature rabbit hippocampal slices.

1. Using the immature (8-12 days postnatal) rabbit hippocampal slice preparation, we investigated regional extracellular potassium concentration [( K+]o) changes that occur during spontaneous and evoked spreading depression (SD) episodes. We report here a difference between the CA1 and CA3 cell populations in the immature hippocampus with regard to 1) resting [K+]o, 2) magnitude of the [K+]o change during seizurelike events and SDs, and 3) susceptibility to SD episodes. Experiments were also performed to elucidate the roles that the Na-K pump and synaptic inhibition play in controlling SD onset, duration, and recovery. We demonstrated a major role for potassium regulation by the Na-K pump and a lesser modulatory role for inhibitory postsynaptic potentials (IPSPs) in preventing SD in the CA3 region. 2. Simultaneous intra- and extracellular recordings were made in the CA1 and CA3 regions of the immature rabbit hippocampus during spontaneous or evoked SD, while potassium ion-sensitive microelectrodes (K-ISMs) monitored changes in [K+]o. The CA1 region had 1) a higher frequency of spontaneous SD episodes than CA3, 2) a lower threshold to potassium-triggered SD, 3) a longer duration SD episode, and 4) smaller post-SD membrane potential and [K+]o undershoots (below the original resting membrane potential and resting [K+]o). 3. During the onset of a SD episode in the CA1 region, the local [K+]o rose either before or at the same time as the membrane potential depolarization. 4. In the CA3 region, spontaneous ictallike events consisting of tonic cell depolarization with repetitive activity followed by clonic afterdischarges were more likely to occur than SD episodes. During these ictallike episodes, [K+]o rose above the 10- to 12-mM ceiling level reported for adult CNS tissue during seizures. Increases in [K+]o evoked by repetitive stimulation were regulated at a lower level in CA3 (average [K+]o rise to 11.4 mM) than in CA1 (average [K+]o rise to 18.3 mM). 5. In CA3, bath application of 10 microM bicuculline or 3.4 mM penicillin did not change the frequency of spontaneously occurring SDs or the SD response threshold to local pressure ejection of 2 M KCl. However, blockade of IPSPs did lead to lower thresholds for SD or seizurelike episodes elicited by stimulation of the mossy fibers. 6. A single application of ouabain (10 microM) to CA3 by local pressure ejection caused a slow rise in local [K+]o measured with K-ISMs. The ouabain treatment also increased the frequency of spontaneous postsynaptic potential activity and decreased the amplitude and duration of CA3 pyramidal cell afterhyperpolarizations (AHPs).(ABSTRACT TRUNCATED AT 400 WORDS)

Duke Scholars

Author Michael Martin Haglund Neurosurgery