Skip to main content
Log in

Inhibitory mechanisms in epileptiform activity induced by low magnesium

  • Original Article
  • Neurophysiology, Muscle and Sensory Organs
  • Published:
Pflügers Archiv Aims and scope Submit manuscript

Abstract

In rat hippocampal slices epileptiform activity was induced by superfusion with Mg2+-free artificial cerebrospinal fluid (ACSF). Paroxysmal depolarization shifts (PDS) were evoked by electrical stimulation of Schaffer collaterals. To investigate the afterpotentials that follow PDS, intracellular recordings were made from CA1 pyramidal cells. The experiments revealed that several components are engaged in the generation of PDS afterpotentials in Mg2+-free ACSF. A long lasting component which determined the overall duration of the PDS afterhyperpolarization was blocked by intracellular application of ethylenebis(oxonitrilo)-tetraacetate (EGTA); concomitantly, the afterhyperpolarizations following depolarizing current injections were blocked. This indicated that the long lasting component was due to a slow Ca2+-activated K+ current. The block of Ca2+-activated K+ current uncovered a depolarizing PDS afterpotential with an N-shaped voltage dependence, suggesting that this depolarizing afterpotential component may be due to an N-methyl d-aspartate (NMDA) conductance. Intracellular injection of Cl revealed that the PDS were followed by Cl currents lasting about 500 ms. This component could be blocked by application of bicuculline suggesting that it is due to a synaptically GABA-mediated (i.e. γ-aminobutyric acid) Cl current. A comparison of PDS afterpotentials in Mg2+-free ACSF and those in other models of epileptiform activity suggests that similar sequences of inhibitory components are activated in spite of different pharmacological alterations of membrane conductances which induce the epileptiform discharges.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Adams PR, Galvan M (1986) Voltage-dependent currents of vertebrate neurons and their role in membrane excitability. Adv Neurol 44:137–170

    Google Scholar 

  2. Alger BE, Nicoll RA (1980) Epileptiform burst afterhyperpolarization: calcium-dependent potassium potential in hippocampal CA1 pyramidal cells. Science 210:1122–1124

    Google Scholar 

  3. Alger BE, Nicoll RA (1980) Spontaneous inhibitory post-synaptic potentials in hippocampus: mechanism for tonic inhibition. Brain Res 200:195–200

    Google Scholar 

  4. Alger BE, Nicoll RA (1982) Pharmacological evidence for two kinds of GABA receptor on rat hippocampal pyramidal cells studied in vitro. J Physiol (Lond) 328:125–141

    Google Scholar 

  5. Alger BE, Williamson A (1988) A transient calcium-dependent potassium component of the epileptiform burst afterhyperpolarization in rat hippocampus. J Physiol (Lond) 399:191–205

    Google Scholar 

  6. Avoli M, Olivier A (1989) Electrophysiological properties and synaptic responses in the deep layers of human epileptic neocortex in vitro. J Neurophysiol 61:589–606

    Google Scholar 

  7. Bader CR, Bertrand D, Schlichter R (1987) Calcium-activated chloride current in cultured sensory and para-sympathetic quail neurones. J Physiol (Lond) 394:125–148

    Google Scholar 

  8. Bowery NG, Price GW, Hudson AL, Hill DR, Wilkin GP, Turnbull MJ (1984) GABA receptor multiplicity: visualization of different receptor types in the mammalian CNS. Neuropharmacology 23:219–231

    Google Scholar 

  9. Collingridge GL, Herron CE, Lester RAJ (1988) Synaptic activation of N-methyl-D-aspartate receptors in the Schaffer collateral-commisural pathway of rat hippocampus. J Physiol (Lond) 399:283–300

    Google Scholar 

  10. Connors BW, Gutnick MJ, Prince DA (1982) Electrophysiological properties of neocortical neurons in vitro. J Neurophysiol 48:1302–1320

    Google Scholar 

  11. Dingledine R (1983) N-Methyl-d-aspartate activates voltage-dependent calcium conductance in rat hippocampal pyramidal cells. J Physiol (Lond) 343:385–405

    Google Scholar 

  12. Domann R, Dorn T, Witte OW (1989) Calcium-dependent potassium current following penicillin-induced epileptiform discharges in the hippocampal slice. Exp Brain Res 78:646–648

    Google Scholar 

  13. Domann R, Dorn T, Witte OW (1991) Afterpotentials following penicillin-induced paroxysmal depolarizations in rat hippocampal CA1 pyramidal cells in vitro. Pflügers Arch 417:469–478

    Google Scholar 

  14. Domann R, Dorn T, Witte OW (1991) Participation of interneurons in penicillin-induced epileptic discharges. Exp Brain Res 83:683–686

    Google Scholar 

  15. Fisher RS (1989) Animal models of the epilepsies. Brain Res Brain Res Brain Res Rev 14:245–278

    Google Scholar 

  16. Hablitz JJ (1981) Effects of intracellular injections of chloride and EGTA on post epileptiform-burst hyperpolarization in hippocampal neurons. Neurosci Lett 22:159–163

    Google Scholar 

  17. Hablitz JJ (1982) Conductance changes induced by DL-homocysteic acid and N-methyl-DL-aspartic acid in hippocampal neurons. Brain Res 247:149–153

    Google Scholar 

  18. Harris RA, Allen AM (1985) Functional coupling of gamma-aminobutyric acid receptors to chloride channels in brain membranes. Science 228:1108–1110

    Google Scholar 

  19. Hestrin S, Nicoll RA, Perkel DJ, Sah P (1990) Analysis of excitatory synaptic action in pyramidal cells using whole-cell recording from rat hippocampal slices. J Physiol (Lond) 422:203–255

    Google Scholar 

  20. Jefferys J, Haas H (1982) Synchronized bursting of CA1 hippocampal cells in the absence of synaptic transmission. Nature 300:448–450

    Google Scholar 

  21. Knowles WD, Schneiderman JH, Wheal HV, Stafstrom CE, Schwartzkroin PA (1984) Hyperpolarizing potentials in guinea pig hippocampal CA3 neurons. Cell Mol Neurobiol 4:207–230

    Google Scholar 

  22. Konnerth A, Keller BU, Ballanyi K, Yaari Y (1990) Voltage sensitivity of NMDA-receptor mediated postsynaptic currents. Exp Brain Res 81:209–212

    Google Scholar 

  23. Lambert JDC, Heinemann U (1986) Aspects of the action of excitatory amino acids on hippocampal CA1 neurons. In: Heinemann U, Klee M, Neher E, Singer W (eds) Calcium electrogenesis and neuronal functioning. Springer, Berlin Heidelberg New York, pp 279–290

    Google Scholar 

  24. Lancaster B, Nicoll RA (1987) Properties of two calcium-activated hyperpolarizations in rat hippocampal neurones. J Physiol (Lond) 389:187–203

    Google Scholar 

  25. Lux HD, Heinemann U (1983) Consequences of calcium-electrogenesis for the generation of paroxysmal depolarization shift. In: Speckmann E-J, Elger CE (eds) Epilepsy and motor system. Urban, Munich, pp 100–119

    Google Scholar 

  26. Macdonald RL, Barker JL (1988) Specific antagonism of GABA-mediated postsynaptic inhibition in cultured mammalian spinal cord neurons: a common mode of convulsant action. Neurology 28:325–330

    Google Scholar 

  27. MacDonald JF, Porietis AV, Wojtowicz JM (1982) L-Aspartic acid induces a region of negative slope conductance in the current-voltage relationship of cultured spinal cord neurons. Brain Res 237:248–253

    Google Scholar 

  28. Matsumoto H, Ajmone-Marsan C (1964) Cortical cellular phenomena in experimental epilepsy: interictal manifestations. Exp Neurol 9:286–304

    Google Scholar 

  29. Mayer ML (1985) A calcium activated chloride current generates the afterdepolarization of rat sensory neurons in culture. J Physiol (Lond) 364:217–239

    Google Scholar 

  30. Mayer ML, Westbrook GL, Guthrie PB (1984) Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurons. Nature 309:261–263

    Google Scholar 

  31. McCormick DA (1989) GABA as an inhibitory neuro-transmitter in human cerebral cortex. J Neurophysiol 62:1018–1027

    Google Scholar 

  32. McCormick DA, Connors BW, Lighthall JW, Prince DA (1985) Comparative electrophysiology of pyramidal and sparsely spiny stellate neurons of the neocortex. J Neurophysiol 54:782–806

    Google Scholar 

  33. Mody I, Lambert JDC, Heinemann U (1987) Low extracellular magnesium induces epileptiform activity and spreading depression in rat hippocampal slices. J Neurophysiol 57:869–888

    Google Scholar 

  34. Newberry NR, Nicoll RA (1984) A bicuculline-resistant inhibitory post-synaptic potential in rat hippocampal pyramidal cells in vitro. J Physiol (Lond) 348:239–254

    Google Scholar 

  35. Schwartzkroin PA (1975) Characteristics of CA1 neurons recorded intracellularly in the hippocampal in vitro slice preparation. Brain Res 85:423–436

    Google Scholar 

  36. Segal M, Barker JL (1984) Rat hippocampal neurons in culture: properties of GABA-activated Cl ion conductance. J Neurophysiol 51:500–515

    Google Scholar 

  37. Simmonds MA (1980) Evidence that bicuculline and picrotoxin act at separate sites to antagonize gamma-aminobutyric acid in rat cuneate nucleus. Neuropharmacology 19:39–44

    Google Scholar 

  38. Speckmann E-J, Witte OW, Walden J (1986) Involvement of calcium ions in focal epileptic activity of the neocortex. In: Heinemann U, Klee M, Neher E, Singer W (eds) Calcium electrogenesis and neuronal functioning. Springer. Berlin Heidelberg New York, pp 386–395

    Google Scholar 

  39. Swann JW, Brady RJ (1984) Penicillin-induced epileptogenesis in immature rat CA3 hippocampal pyramidal cells. Dev Brain Res 12:243–254

    Google Scholar 

  40. Tancredi V, Avoli M, Hwa GGC (1988) Low-magnesium epilepsy in rat hippocampal slices: inhibitory postsynaptic potentials in the CA1 subfield. Neurosci Lett 89:293–298

    Google Scholar 

  41. Tancredi V, Hwa GGC, Zona C, Brancati A, Avoli M (1990) Low magnesium epileptogenesis in the rat hippocampal slice: electrophysiological and pharmalogical features. Brain Res 511:280–290

    Google Scholar 

  42. Witte OW (1994) Afterpotentials of penicillin-induced epileptiform neuronal discharges in the motor cortex of the rat in vivo. Epilepsy Res 18:43–55

    Google Scholar 

  43. Wong RKS, Prince RD (1978) Participation of calcium spikes during intrinsic burst firing in hippocampal neurons. Brain Res 159:385–390

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Westerhoff, C.H.A., Domann, R. & Witte, O.W. Inhibitory mechanisms in epileptiform activity induced by low magnesium. Pflügers Arch. 430, 238–245 (1995). https://doi.org/10.1007/BF00374655

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00374655

Key words

Navigation