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

Abstract

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)

Mutation I810N in the α3 isoform of Na + ,K + -ATPase causes impairments in the sodium pump and hyperexcitability in the CNS

“…The loss of ␣3 Na ϩ ,K ϩ -ATPase activity might induce neuronal membrane depolarization accompanied by hyperexcitability through an increase of the extracellular K ϩ concentration because of the deficient clearance by the Na ϩ ,K ϩ -pump (4,5). Although the ␣2-isoform of Na ϩ ,K ϩ -ATPase present in glial cells has been promoted as the major isoform involved in K ϩ clearance, there are indications that neuronal Na ϩ ,K ϩ -ATPase could be more important than glial Na ϩ ,K ϩ -ATPase for K ϩ clearance after epileptiform activity induced in hippocampal slices (8).…”

“…Na ϩ ,K ϩ -ATPases (sodium/potassium pumps) play a seminal role in controlling neuronal excitability by maintaining electrochemical gradients for Na ϩ and K ϩ across the plasma membrane. Hence, it has been hypothesized that an abnormality in Na ϩ ,K ϩ -ATPase could facilitate seizures (3)(4)(5)(6). Indeed, partial inhibition of Na ϩ ,K ϩ -ATPase activity with cardiac glycosides has been shown to induce seizures in rats (7)(8)(9).…”

Changes in Hippocampal Neuronal Activity During and After Unilateral Selective Hippocampal IschemiaIn Vivo

“…The cessation of the activity was accompanied by a similar short period high-frequency (25-50 Hz) spindle. High-frequency electrical activity, synaptic noise, and impulse firing precede the DC voltage shift of the spreading depression as observed in cells in the hippocampus and neocortex (Rosenblueth and García Ramos, 1966;Ichijo and Ochs, 1970;Munoz-Martinez, 1970;Higashida et al, 1974;Somjen and Aitken, 1984;Haglund and Schwartzkroin, 1990). Lasting oscillations at high frequencies (200 -600 Hz) have been recorded in normal neocortex, but hippocampal "pathological high-frequency oscillations" probably represent field potentials of population spikes from clusters of synchronous pathologically bursting cells (Engel, Jr. et al, 2009).…”

Development of GABA‐mediated, chloride‐dependent inhibition in CA1 pyramidal neurones of immature rat hippocampal slices.

“…1989). Because of the ATPdependence of GABA currents (Stelzer et al 1988;Chen et al 1990) and transmembrane K+ and Na+ gradients (Haglund & Schwartzkroin, 1990), no attempt was made in these experiments to examine the possible contribution of the ATPdriven Cl-pump in the maintenance of low [Cl-] (Table 1), older neurones showed a decreased input resistance, in keeping with the reported increased size of the soma and dendritic tree with development (Pokorny & Yamamoto, 1981;Schwartzkroin, 1982), although decreased specific membrane resistance from increased ionic permeability is also possible (Carlen & Durand, 1981). The ionic exchange between the patch pipette and cytoplasm is not instantaneous, but has a time constant of several seconds (Fenwick, Marty & Neher, 1982 (Huguenard & Alger, 1986;Akaike et al 1987) is possibly due in part to the presence of strong active Cl-extrusion systems in the older CAl neurones in the slice preparation.…”

“…The ionic exchange between the patch pipette and cytoplasm is not instantaneous, but has a time constant of several seconds (Fenwick, Marty & Neher, 1982 (Huguenard & Alger, 1986;Akaike et al 1987) is possibly due in part to the presence of strong active Cl-extrusion systems in the older CAl neurones in the slice preparation. Also, the efficiency of metabolically dependent Cl-transport mechanisms may be decreased in acutely dissociated neurones (Huguenard & Alger, 1986 (Haglund & Schwartzkroin, 1990), suggesting the development of active ionic extrusion systems during this period.…”