Activity- and pH-dependent adenosine shifts at the end of a focal seizure in the entorhinal cortex

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Abstract

Adenosine (ADO) is an endogenous modulator of neuronal excitability, with anticonvulsant and neuroprotective effects. It has been proposed that the activity-dependent release of ADO promoted by the extracellular acidification occurring during seizures contributes to seizure termination. To verify this hypothesis, we recorded field potentials, pH and ADO changes measured with enzymatic biosensors during acute focal seizures in the medial entorhinal cortex (mEC) of the isolated guinea-pig brain maintained in vitro. The effect of ADO on seizure-like events (SLEs) induced by GABAa receptor antagonism with bicuculline methiodide (BMI; 50 μM) was assessed by arterial applications of 1 mM ADO. ADO either reduced or prevented epileptiform activity. The A1 receptor antagonist DPCPX (100–500 μM) prolonged BMI-induced seizures and was able to precipitate SLEs in the absence of proconvulsant. Simultaneous recordings of brain activity, extracellular ADO and pH shifts demonstrated that ADO decreases at the onset and progressively rises toward the end of SLEs induced by either BMI or 4-aminopyridine (4AP; 50 μM), reaching maximal values 1−5 min after SLE termination. ADO changes were preceded by a SLE-dependent extracellular acid shift. Both pH acidification and ADO changes were abolished by 22 mM HEPES in the arterial perfusate. In these conditions, SLE duration was prolonged. Our data confirm that ADO plays a role in regulating brain excitability. Its increase depends on seizure-induced acid pH shift and it is maximal after the end of the SLE. These findings strongly suggest that ADO contributes to termination of focal seizures and to the establishment of the postictal depression.

Original languageEnglish
Article number106401
JournalEpilepsy Research
Volume165
DOIs
Publication statusPublished - Sep 2020

Keywords

  • Acidification
  • Adenosine
  • Entorhinal cortex
  • Isolated guinea-pig brain
  • Seizure termination

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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