Research report
Alterations in the microenvironment during spreading depression associated with epileptiform activity in the immature neocortex

https://doi.org/10.1016/0165-3806(89)90288-5Get rights and content

Abstract

Local changes in extracellular ion concentrations were measured with ion-sensitive microelectrodes in slices of mature (>40 days of age) or immature (16–30 days of age) rat neocortex maintained in vitro. Repetitive stimulation resulted in increases in extracellular potassium ([K+]o) to levels of 8.85 ± 2.1 mM in slices from adult animals and 12.77 ± 1.8 mM in slices from immature animals. During exposure to picrotoxin, maximum levels were 11.3 ± 2.6 and 14.8 ± 2.5 mM in the mature and immature groups, respectively. Picrotoxin (50 μM) induced spontaneous bursts of repetitive spiking, followed by a slow, negative field potential, associated with spreading depression (SD), in slices from immature animals. [K+]o levels increased to 10.2 ± 3.9 mM during repetitive spike discharges and reached 30.3 ± 18.5 mM during SDs. Variations in the size of the extracellular space (ES) were examined during SD. The ES was found to reversibly decrease by 39 ± 4.5%. Clusters of repetitive spikes were associated with 0.1–0.2 mM decreases in [Ca2+]o, whereas 1.12 ± 0.06 mM decreases were observed during SDs. Decreases in [Na+]o and [Cl-o of 56 ± 10 mM and 41 ± 9 mM, respectively, were observed during SDs suggesting that a net transmembrane movement of water occurred during SDs. These results indicate that changes in [K+]o associated with epileptiform activity in the immature nervous system are quantitatively different from those observed in the mature brain. These large increases in [K+]o may contribute to the prolonged nature of epileptiform discharges in the developing nervous system.

References (49)

  • W. Moody et al.

    Extracellular potassium activity during epileptogenesis

    Exp. Neurol.

    (1974)
  • R. Mutani et al.

    Potassium activity in immature cortex

    Brain Res.

    (1974)
  • R. Pumain et al.

    Chemical synaptic transmission is not necessary for epileptic seizures to persist in the baboon Papio papio

    Exp. Neurol.

    (1985)
  • W. Singer et al.

    Presynaptic depolarization and extracellular potassium in the cat lateral geniculate nucleus

    Brain Res.

    (1973)
  • J.W. Swann et al.

    Extracellular K+ accumulation during penicillin-induced epileptogenesis in the CA3 region of immature rat hippocampus

    Dev. Brain Res.

    (1986)
  • E.C. Zuckermann et al.

    Hippocampal epileptic activity induced by localized ventricular perfusion with high-potassium cerebrospinal fluid

    Exp. Neurol.

    (1968)
  • J. Bures et al.

    The Mechanism of Applications of Leao's Spreading Depression of Electroencephalographic Activity

    (1974)
  • B.W. Connors et al.

    Activity-dependent K+ accumulation in the developing rat optic nerve

    Science

    (1982)
  • I. Dietzel et al.

    Transient changes in the size of extracellular space in the sensorimotor cortex of cats in relation to stimulus-induced changes in potassium concentration

    Exp. Brain Res.

    (1980)
  • B. Grafstein

    Mechanism of spreading cortical depression

    J. Neurophysiol.

    (1956)
  • J.D. Green

    The hippocampus

    Physiol. Rev.

    (1964)
  • M.J. Gutnick et al.

    Mechanisms of neocortical epileptogenesis in vitro

    J. Neurophysiol.

    (1982)
  • J.J. Hablitz

    Picrotoxin-induced epileptiform activity in hippocampus: role of endogenous versus synaptic factors

    J. Neurophysiol.

    (1984)
  • J.J. Hablitz

    Spontaneous ictal-like discharges and sustained potential shifts in the developing rat neocortex

    J. Neurophysiol.

    (1987)
  • Cited by (0)

    Present address: Institut für Normale und Pathologische Physiologie, Universität Köln, D-5000, Köln, F.R.G.

    View full text