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

doi:10.1016/0165-3806(86)90115-X

Developmental Brain Research

Volume 30, Issue 2, December 1986, Pages 243-255

https://doi.org/10.1016/0165-3806(86)90115-X Get rights and content

Abstract

Ion-selective microelectrode techniques were used to study extracellular K⁺ changes associated with penicillin-induced epileptogenesis in the CA₃ region of hippocampal slices. Recordings were made in slices taken from rats 9–16 days of age, which have a pronounced capacty to undergo prolonged synchronized afterdischarges. Direct comparisons were made to slices from hippocampus from more mature rats, 30–35 days old, which are much less prone to seizure-like events. The amplitude and time course of the K⁺ transients varied across the CA₃ laminae. K⁺ signals were largest close to stratum pyramidale in stratum oriens (the infrapyramidal zone). Recordings from this site showed extracellular K⁺ accumulation to be unusually large in immature hippocampus. The ceiling [K⁺]_o level recorded during seizure-like events ranged from 14.4 to 20.2 mM and averaged 16.9 mM. The peak amplitude of extracellular K⁺ transients following an epileptiform burst in slices from immature rats averaged 4.31 mM while the mean of similar recordings from mature rats was 0.97 mM. Detailed laminar distribution studies in developing hippocampus revealed that the K⁺ signals were large in the proximal two-thirds of the basilar dendrites and proximal half of the apical dendrites. K⁺ accumulation in stratum pyramidale was comparatively small even though at its very edge in stratum oriens large K⁺ transients were always recorded. The latter was also true in recordings from mature hippocampus. Other dendritic signals in mature tissue were comparatively small. Laminar analysis was performed of the field potentials recorded by the reference barrel of the K⁺ electrodes. Negative field potential for the epileptiform burst and subsequent slow potential correlated in space with sites of K⁺ accumulation in both immature and mature hippocampal slices. Interictal and prolonged ictal-like discharges, recorded in developing hippocampus, arose from the same baseline [K⁺]_o. However, since [K⁺]_o is excessively high during the course of these epileptiform events it most likely has a role in the unusual propensity of immature hippocampus for seizures.

References (63)

C. Benninger et al.
Extracellular calcium and potassium changes in hippocampal slices
Brain Res.
(1980)
V.F. Castellucci et al.
Contributions to steady potential shifts of slow depolarization in cells presumed to be glia
Electroenceph. Clin. Neurophysiol.
(1970)
M.A. Dichter et al.
Silent cells during interictal discharges and seizures in hippocampal penicillin foci: evidence for the role of extracellular K⁺ in the transition from the interictal state to seizures
Brain Research
(1972)
K.J. Futamachi et al.
Glial cells and extracellular potassium: their relationship in mammalian cortex
Brain Res.
(1976)
J.J. Hablitz
Conductance changes induced by d,l-homocysteic acid and N-methyl-d,l-aspartic acid in hippocampal neurons
Brain Res.
(1982)
U. Heinemann et al.
Undershoots following stimulus-induced rises of extracellular potassium concentration in cerebral cortex of cat
Brain Res.
(1975)
F.A. Henn et al.
Glial cell function: active control of extracellular K⁺ concentration
Brain Res.
(1972)
L. Hertz
An intense potassium uptake into astrocytes, its further enhancement by high concentration of potassium, and its possible involvement in potassium homeostasis at the cellular level
Brain Res.
(1978)
R. Llinas et al.
Calcium conductances in Purkinje cell dendrites: their role in development and integration
W.J. Moody et al.
Extracellular potassium activity during epileptogenesis
Exp. Neurol.
(1974)

S.L. Moshe et al.

Increased seizure susceptability of the immature brain

Brain Res.

(1983)

R. Mutani et al.

Potassium activity in immature cortex

Brain Res.

(1974)

N. Ogata

Ionic mechanisms of the depolarization shift in thin hippocampal slices

Exp. Neurobiol.

(1975)

D.A. Prince et al.

Neuronal activities in epileptogenic foci of immature cortex

Brain Research

(1972)

B.R. Ransom

The behavior of presumed glial cells during seizure discharge in cat cerebral cortex

Brain Res.

(1974)

P.A. Schwartzkroin et al.

Recordings from presumed glial cells in the hippocampal slice

Brain Res.

(1979)

J.W. Swann et al.

Penicillin-induced epileptogenesis in immature rat CA₃ hippocampal pyramidal cells

Dev. Brain Res.

(1984)

F. Vyskocil et al.

Potassium-selective microelectrodes used for the extracellular brain potassium during spreading depression and anoxic depolarization in rats

Brain Res.

(1972)

F.S. Wright et al.

Maturation of epileptiform activity

Electroenceph. Clin. Neurophysiol.

(1968)

A.A. Abdel-Latif et al.

Studies on sodium-potassium adenosine triphosphatase of the nerve endings and appearance of electrical activity in developing rat brain

J. Neurochem.

(1967)

M. Baudry et al.

Classification and properties of amino acid receptors in hippocampus: supersensitivity during the postnatal period and following denervation

Mol. Pharmacol.

(1983)

W. Bondareff et al.

Distribution of the extracellular space during postnatal maturation of rat cerebral cortex

Anat. Rec.

(1968)

R.J. Brady et al.

Increase in extracellular K⁺ and negative fields produced by glutamate in hippocampal slices

Soc. Neurosci. Abstr.

(1984)

M.W. Cohen

The contribution of glial cells to surface recordings from the optic nerve of an amphibian

J. Physiol. (London)

(1970)

M.W. Cohen

Glial potentials and their contribution to extracellular recordings

B.E. Connors et al.

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

Science

(1982)

R.S. Fisher et al.

The role of extracellular potassium in hippocampal epilepsy

Arch. Neurol.

(1976)

R.K. Ferguson et al.

Penetration of 14C-inulin and 14C-sucrose into the brain, cerebrospinal fluid, and skeletal muscle of developing rats

Exp. Brain Res.

(1969)

A.R. Gardner-Medwin et al.

Changes of extracellular potassium activity induced by electric current through brain tissue in the rat

J. Physiol. (London)

(1983)

J.D. Green

The hippocampus

Physiol. Rev.

(1964)

J.J. Hablitz et al.

Excitation of hippocampal pyramidal cells by glutamate in the guinea-pig and rat

J. Physiol. (London)

(1982)

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^☆: An abstract of this work has already been published (see ref. 51).

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

Abstract

Brain Res.

Electroenceph. Clin. Neurophysiol.

Brain Research

Brain Res.

Brain Res.

Brain Res.

Brain Res.

Brain Res.

Exp. Neurol.

Brain Res.

Brain Res.

Exp. Neurobiol.

Brain Research

Brain Res.

Brain Res.

Dev. Brain Res.

Brain Res.

Electroenceph. Clin. Neurophysiol.

Studies on sodium-potassium adenosine triphosphatase of the nerve endings and appearance of electrical activity in developing rat brain

J. Neurochem.

Classification and properties of amino acid receptors in hippocampus: supersensitivity during the postnatal period and following denervation

Mol. Pharmacol.

Distribution of the extracellular space during postnatal maturation of rat cerebral cortex

Anat. Rec.

Increase in extracellular K+ and negative fields produced by glutamate in hippocampal slices

Soc. Neurosci. Abstr.

The contribution of glial cells to surface recordings from the optic nerve of an amphibian

J. Physiol. (London)

Glial potentials and their contribution to extracellular recordings

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

Science

The role of extracellular potassium in hippocampal epilepsy

Arch. Neurol.

Penetration of 14C-inulin and 14C-sucrose into the brain, cerebrospinal fluid, and skeletal muscle of developing rats

Exp. Brain Res.

Changes of extracellular potassium activity induced by electric current through brain tissue in the rat

J. Physiol. (London)

The hippocampus

Physiol. Rev.

Excitation of hippocampal pyramidal cells by glutamate in the guinea-pig and rat

J. Physiol. (London)

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

Increase in extracellular K⁺ and negative fields produced by glutamate in hippocampal slices

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