Pflügers Archiv

, Volume 398, Issue 4, pp 310–317 | Cite as

Changes in [Ca2+]o and [K+]o during repetitive electrical stimulation and during pentetrazol induced seizure activity in the sensorimotor cortex of cats

  • Uwe Heinemann
  • Jacques Louvel
Excriable Tissues and Contral Nervous Physiology


Changes in [Ca2+]o and [K+]o were measured in the sensorimotor cortex of cats during repetitive electrical stimulation and during pentetrazol induced epileptiform activity. Repetitive stimulation of the thalamic ventrobasal complex (VB) or of the cortical surface (CS) caused decreases in [Ca2+]o by up to 0.45 mM and increases in [K+]o by up to 7 mM. Maximum reductions of [Ca2+]oΔ[Ca2+]o were found in depths of 100 to 300 μm below cortical surface, while rises in [K+]o were largest in depths of 600 to 1000 μm dependent on stimulation site. At depths below 700–900 μm increases in [K+]o were often accompanied by rises in [Ca2+]o of about 0.2 mM. Pentetrazol (PTZ) when injected at doses of 25 to 40 mg/kg body weight induced spontaneous seizure activity, which was in about 40% preceeded by a slight fall of baseline [Ca+]o. Repetitive stimulation and spontaneous seizures resulted in Δ[Ca2+]o of up to 0.6 mM, whereas rises in [K+]o remained limited to a ‘ceiling level’ of about 10 mM. After PTZ application, peak Δ[Ca2+]o were found at the same recording sites, but, in contrast to normal cortex, decreases in [Ca2+]o were observed in all cortical layers. The enhanced Ca2+-signals after PTZ application and the observed reductions of [Ca2+]o before seizure onset suggest that PTZ utilizes Ca2+-dependent mechanisms to initiate seizure activity.

Key words

[K+]o−[Ca2+]o Electrical stimulation Pentetrazol Epilepsy Sensorimotor cortex 


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  1. Agnew WF, Yuen TGH, Bullara LA, Jacques D, Pudenz RH (1979) Intracellular calcium deposition in brain following electrical stimulation. Neurol Res 1:187–202Google Scholar
  2. Ammann D, Meier PC, Simon W (1979) Design and use of Ca2+ selective microelectrodes. In: Ashley CC, Campbell AK (eds) Detection and measurement of free calcium ions in cells. Elsevier, Amsterdam, pp 117–132Google Scholar
  3. Antoniadis A, Mueller WE, Wollert U (1980) Inhibition of GABA and benzodiazepine receptor binding by penicillin. Neurosci Lett 18:309–312Google Scholar
  4. Benninger C, Kadis J, Prince DA (1980) Extracellular calcium and potassium changes in hippocampal slices. Brain Res 187:165–182Google Scholar
  5. Cordingley GE, Somjen GG (1978) Dissipation of locally accumulated extracellular potassium in the cat cerebral cortex. Brain Res 151:291–306Google Scholar
  6. David RJ, Wilson WA, Escueta AV (1974) Voltage clamp analysis of pentylenetetrazole effects on aplysia neurons. Brain Res 67:549–554Google Scholar
  7. Dietzel I, Heinemann U, Hofmeier G, Lux HD (1980) Transient changes in the size of the extracellular space in the sensorimotor cortex of cats in relation to stimulus induced changes in potassium concentration. Exp Brain Res 40:432–439Google Scholar
  8. Dietzel I, Heinemann U, Hofmeier G, Lux HD (1982) Stimulus-induced changes in extracellular Na+ and Cl concentration in relation to changes in the size of the extracellular space. Exp Brain Res 46:73–84Google Scholar
  9. Dunlap K, Fischbach GD (1978) Neurotransmitters decrease the calcium component of sensori neurone action potentials. Nature 376:837–839Google Scholar
  10. Galvan M, Grafe P, Bruggencate G ten (1982) Convulsive actions of 4-aminopyridine on neurones and extracellular K+ and Ca2+ activites in guinea-pig olfactory cortex slices. In: Klee MR, Lux HD, Speckmann EJ (eds) Pharmacology and physiology of epileptogenic phenomena. Raven Press, New York, pp 353–360Google Scholar
  11. Gutnick MJ, Heinemann U, Lux HD (1979) Stimulus induced and seizure related changes in extracellular potassium concentration in cat thalamus (VPL). Electroencephalogr Clin Neurophysiol 47:329–344Google Scholar
  12. Hassler R, Muhs-Clement K (1964) Architektonischer Aufbau des sensomotorischen und parietalen Cortex der Katze. J Hirnforsch 6:377–420Google Scholar
  13. Heinemann U, Gutnick MJ (1979) Relation between extracellular potassium concentration and neuronal activities in cat thalamus (VPL) during projection of cortical epileptiform discharge. Electroencephalogr Clin Neurophysiol 47:345–357Google Scholar
  14. Heinemann U, Lux HD (1975) Undershoots following stimulus induced rises of extracellular potassium concentration in cerebral cortex of cat. Brain Res 93:63–76Google Scholar
  15. Heinemann U, Lux HD (1977) Ceiling of stimulus induced rises in extracellular potassium concentration in the cerebral cortex of cats. Brain Res 120:231–249Google Scholar
  16. Heinemann U, Lux HD (1983) Ionic changes during experimentally induced epilepsies. In: Rose FC (ed) Progress in epilepsy. Pitman Medical London, pp 87–102Google Scholar
  17. Heinemann U, Pumain R (1980) Extracellular calcium activity changes in cat sensorimotor cortex induced by iontophoretic application of amino acids. Exp Brain Res 40:247–250Google Scholar
  18. Heinemann U, Pumain R (1981) Effects of tetrodotoxin on changes in extracellular free calcium induced by repetitive electrical stimulation and iontophoretic application of excitatory amino acids in the sensorimotor cortex of cats. Neurosci Lett 21:87–91Google Scholar
  19. Heinemann U, Lux HD, Gutnick MJ (1977) Extracellular free calcium and potassium during paroxysmal activity in cerebral cortex of the cat. Exp Brain Res 27:237–243Google Scholar
  20. Heinemann U, Lux HD, Gutnick MJ (1978) Changes in extracellular free calcium and potassium activity in the somatosensory cortex of cats. In: Chalazonitis M, Boisson M (eds) Abnormal neuronal discharges. Raven Press, New York, pp 329–345Google Scholar
  21. Heinemann U, Konnerth A, Lux HD (1981) Stimulation induced changes in extracellular free calcium in normal cortex and chronic alumnia cream foci of cats. Brain Res 213:246–250Google Scholar
  22. Heinemann U, Konnerth A, Louvel J, Lux HD, Pumain R (1982). Changes in extracellular free Ca2+ in normal and epileptic sensorimotor cortex of cats. In: Klee MR, Lux HD, Speckmann EJ (eds) Physiology and pharmacology of epileptogenic phenomena. Raven Press. New York, pp 29–35Google Scholar
  23. Hofmeier G, Lux HD (1982) The depolarizing actionof calcium injected into snail neurones — a mechanism contributing to epileptogenesis? In: Klee MR, Lux HD, Speckman EJ (eds) Physiology and pharmacology of epileptogenic phenomena. Raven Press, New York, pp 299–308Google Scholar
  24. Hotson JR (1982) Barium and penicillin: two prototypes of epileptiform burst generation in hippocampal neurons. In: Klee MR, Lux HD, Speckmann EJ (eds) Physiology and pharmacology of epileptogenic phenomena. Raven Press, New York, pp 113–121Google Scholar
  25. Jefferys JGR, Haas HL (1982) Synchronized bursting of CA1 hippocampal pyramidal cells in the absence of synaptic transmission. Nature 300:448–450Google Scholar
  26. Katz B, Miledi R (1969) Tetrodotoxin-resistant electrical activity in presynaptic terminals. J Physiol 203:459–487Google Scholar
  27. Klee MR, Faber DS, Heiss WD (1973) Strychnine- and pentylenetetrazol-induced changes of excitability in Aplysia neurons. Science 179:1133–1136Google Scholar
  28. Konnerth A, Heinemann U, Yaari Y (1983) Transmission of neural activity in hippocampal area CA1 in the absence of active chemical synapses. Nature (in press)Google Scholar
  29. Llinas R, Sugimori M (1980) Electrophysiological properties of ‘in vitro’ Purkinje cell dendrites in mammalian cerebellar slices. J Physiol 305:197–213Google Scholar
  30. Louvel J, Aldenhoff J, Hofmeier C, Heinemann U (1982) Effects of the convulsant drug oenanthotoxin on snail neurones and on cat cortex. In: Klee MR, Lux HD, Speckmann EJ (eds) Physiology and pharmacology of epileptogenic phenomena. Raven Press, New York, pp 47–52Google Scholar
  31. Louvel J, Heinemann U (1981) Mode d'action des agents epileptogenes au niveau cellulaire. Rev EEG Neurophysiol (Paris) 11:335–339Google Scholar
  32. Lux HD (1974) Kinetics of extracellular potassium relation to epileptogenesis. Epilepsia 15:375–393Google Scholar
  33. Lux HD, Heinemann U (1982) Consequences of calcium-electrogenesis for the generation of paroxysmal depolarisation shift. In: Speckmann EJ, Elger H (eds) Epilepsy and motor system. Urban and Schwarzenberg, München, pp 100–119Google Scholar
  34. Lux HD, Neher E (1973) The equilibration time course of [K+]o in cat cortex. Exp Brain Res 17:190–205Google Scholar
  35. Mac Donald RL, Barker JL (1977) Pentylenetetrazol and penicillin are selective antagonists of GABA-mediated postsynaptic inhibition in cultured mammalian neurones. Nature 267:720–721Google Scholar
  36. Macon JB, King DW (1979) Responses of somatosensory cortical neurons to inhibitory amino acids during topical and iontophoretic application of epileptogenic agents. Electroencephalogr Clin Neurophysiol 47:41–51Google Scholar
  37. Mares J, Mares P, Trojan S (1980) The ontogenesis of cortical self-sustained after-discharges in rats. Epilepsia 21:111–121Google Scholar
  38. Moody W, Futamachi KJ, Prince DA (1974) Extracellular potassium activity during epileptogenesis. Exp Neurol 42:248–263Google Scholar
  39. Nicholson C (1980) Dynamics of the brain cell microenvironment. NRP-Bull 18:1–113Google Scholar
  40. Nicholson C, Bruggencate G ten, Stoeckle H, Steinberg R (1978) Calcium and potassium changes in extracellular microenvironment of cat cerebellar cortex. J Neurophysiol 41:1026–1039Google Scholar
  41. Oehme M, Kessler M, Simon W (1976) Neutral carrier Ca++-microelectrode. Chimia 30:204–206Google Scholar
  42. Orkand RK, Nicholls JG, Kuffler SW (1966) Effect of nerve impulses on the membrane potential of glial cells in the central nervous system of amphibia. J Neurophysiol 29:788–806Google Scholar
  43. Pellmar TC, Wilson WA (1977) Synaptic mechanism of pentylenetetrazole: selectivity for chloride conductance. Science 197:912–914Google Scholar
  44. Pumain R, Heinemann U (1982) Intracellular potential and extracellular calcium changes in chronic epilepsy. In: Akimoto H, Kazamatzuri H, Seino M, Ward A (eds) Advances in epileptology; XIIIth Epilepsy International Symposium. Raven Press, New York, pp 497–500Google Scholar
  45. Schwartzkroin PA, Pedley TA (1979) Slow depolarizing potential in “epileptic neurons”. Epilepsia 20:267–277Google Scholar
  46. Schwartzkroin PA, Prince DA (1980) Changes in excitatory and inhibitory synaptic potentials leading to epileptogenic activity. Brain Res 183:61–76Google Scholar
  47. Schwartzkroin PA, Slawsky M (1977) Probable calcium spikes in hippocampal neurons. Brain Res 135:157–161Google Scholar
  48. Schwindt PC, Crill WE (1980a) Role of a persistent inward current in motoneuron bursting during spinal seizures. J Neurophysiol 43:1296–1318Google Scholar
  49. Schwindt PC, Crill WE (1980b) Properties of a persistent inward current in normal and TEA-injected motoneurons. J Neurophysiol 43:1700–1724Google Scholar
  50. Somjen CG (1980) Stimulus-evoked and seizure-related responses of extracellular calcium activity in spinal cord compared to those in cerebral cortex. J Neurophysiol 44:617–632Google Scholar
  51. Speckmann EJ, Caspers H (1973) Paroxysmal depolarization and changes in action potentials induced by pentylenetetrazol in isolated neurons of Helix pomatia. Epilepsia 14:397–408Google Scholar
  52. Sugaya F, Onuzuka M, Furuichi H, Sugaya A, Tsuda T (1982) Intracellular calcium and bursting activity. In: Klee MR, Lux HD, Speckmann EJ (eds), Pharmacology and physiology of epileptogenic phenomena. Raven Press, New York, pp 325–334Google Scholar
  53. Vern BA, Schuette WH, Thibault CE (1977) [K+]o clearance in cortex: a new analytical model. J Neurophysiol 40:1015–1023Google Scholar
  54. White EL (1979) Thalamocortical synaptic relations: a review with emphasis on the projections of specific thalamic nuclei to the primary sensory areas of the neocortex. Brain Res Rev 1:275–311Google Scholar
  55. Wilson WA, Escueta AV (1974) Common synaptic effects of pentylenetetrazol and penicillin. Brain Res 72:168–171Google Scholar
  56. Wong RKS, Prince DA (1979) Dendritic mechanisms underlying penicillin-induced epileptiform activity. Science 204:1228–1231Google Scholar
  57. Woodbury DM (1980) Convulsant drugs: Mechanisms of actions. In: Glaser GM, Penry JK, Woodbury DM (eds) Antiepileptic drugs: Mechanisms of action. Raven Press, New York, pp 249–302Google Scholar
  58. Yaari Y, Konnerth A, Heinemann U (1983) Spontaneous epileptiform activity of CA1 hippocampal neurones in low extracellular calcium solutions. Exp Brain Res (in press)Google Scholar
  59. Zanotto L, Heinemann U (1983) Aspartate and glutamate induced reductions in extracellular free calcium and sodium concentration in area CA1 of “in vitro” hippocampal slices of rats. Neurosci Lett 35:79–84Google Scholar

Copyright information

© Springer-Verlag 1983

Authors and Affiliations

  • Uwe Heinemann
    • 1
  • Jacques Louvel
    • 1
  1. 1.Abteilung NeurophysiologieMax Planck Institut für PsychiatrieMünchen 40Federal Republic of Germany

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