PURPOSE: Epileptiform burst-firing can occur in hippocampal area CA1 where recurrent excitation is relatively weak and recurrent inhibition strong. Recent observations suggest that recurrent inhibition can transform into recurrent excitation because of collapse of the chloride gradient. Here we assess the role of potassium in this epileptogenic transformation. METHODS: Extracellular field potential recordings, combined with either intracellular recordings from pyramidal neurons or extracellular potassium concentration recordings, were made in vitro from isolated CA1 minislices cut from the rat hippocampus and in vivo from area CA1 in urethane-anesthetized rats. Burst responses were evoked by 5-Hz alveus stimulation. RESULTS: The 5-Hz alveus stimulation in vitro caused a transient period of burst responses that was associated with a transient increase in synaptic input in stratum oriens and a transient shift of the reversal potential of the synaptic potential. These changes were related to the transient increase in extracellular potassium concentration in stratum oriens. Observations in vivo confirmed the relation between bursting and extracellular potassium concentration in stratum oriens. CONCLUSIONS: Use-dependent increase of extracellular potassium concentration in stratum oriens facilitates the collapse of the chloride gradient in the basal dendrites and transforms gamma-aminobutyric acid (GABA)ergic inhibition into GABAergic excitation, giving rise to burst firing. Improvement of intracellular chloride homeostasis or extracellular potassium homeostasis could reduce epileptogenicity.
PURPOSE: Epileptiform burst-firing can occur in hippocampal area CA1 where recurrent excitation is relatively weak and recurrent inhibition strong. Recent observations suggest that recurrent inhibition can transform into recurrent excitation because of collapse of the chloride gradient. Here we assess the role of potassium in this epileptogenic transformation. METHODS: Extracellular field potential recordings, combined with either intracellular recordings from pyramidal neurons or extracellular potassium concentration recordings, were made in vitro from isolated CA1 minislices cut from the rat hippocampus and in vivo from area CA1 in urethane-anesthetized rats. Burst responses were evoked by 5-Hz alveus stimulation. RESULTS: The 5-Hz alveus stimulation in vitro caused a transient period of burst responses that was associated with a transient increase in synaptic input in stratum oriens and a transient shift of the reversal potential of the synaptic potential. These changes were related to the transient increase in extracellular potassium concentration in stratum oriens. Observations in vivo confirmed the relation between bursting and extracellular potassium concentration in stratum oriens. CONCLUSIONS: Use-dependent increase of extracellular potassium concentration in stratum oriens facilitates the collapse of the chloride gradient in the basal dendrites and transforms gamma-aminobutyric acid (GABA)ergic inhibition into GABAergic excitation, giving rise to burst firing. Improvement of intracellular chloride homeostasis or extracellular potassium homeostasis could reduce epileptogenicity.
Authors: John G R Jefferys; Liset Menendez de la Prida; Fabrice Wendling; Anatol Bragin; Massimo Avoli; Igor Timofeev; Fernando H Lopes da Silva Journal: Prog Neurobiol Date: 2012-03-07 Impact factor: 11.685
Authors: Katerina Hristova; Cristina Martinez-Gonzalez; Thomas C Watson; Neela K Codadu; Kevan Hashemi; Peter C Kind; Matthew F Nolan; Alfredo Gonzalez-Sulser Journal: Brain Date: 2021-06-22 Impact factor: 15.255