GABAergic inhibition and the induction of spontaneous epileptiform activity by low chloride and high potassium in the hippocampal slice.
Intracellular recordings from CA3b/c neurons in rat hippocampal slices showed that reduction of the extracellular Cl- concentration from 136 to 53 mM produced a positive (+10 mV) shift in the reversal potential of GABAergic inhibitory postsynaptic potentials (IPSPs). This shift was not significantly different from the shift produced by raising K+ from 3.5 to 8.5 mM. Spontaneous interictal bursting occurred in both low Cl- and high K+. Extracellular recordings from the pyramidal cell layer in the CA3b/c region of hippocampal slices showed that bursts in 56 mM Cl- were of the same waveform and intensity as bursts produced by high K+. However the frequency of spontaneous bursting was much lower (6.6 +/- 1.2/min, n = 10) in low Cl- compared to high K+ (42.2 +/- 3.0/min, n = 33). Burst frequency was a linear function of the shift in IPSP reversal potential produced by high K+, but not low Cl-. Replacing 60% of the Cl- with methylsulfate or isethionate was sufficient to produce spontaneous bursting, whereas it was necessary to replace 80% of the Cl- when propionate was used as a substitute. All 3 Cl- substitutes lowered the ionized Ca2+ concentration, but raising the extracellular Ca2+ concentration back to normal did not change the burst frequency. Since the amplitude of IPSPs is reduced to a similar extent in low Cl- and high K+ solutions, whereas bursting is much faster in high K+, we suggest that impaired GABAergic inhibition is insufficient to fully account for spontaneous interictal bursting that is produced in hippocampal slices by raised extracellular K+.
Chamberlin
N L
NL
Department of Pharmacology, University of North Carolina, Chapel Hill 27514.
Dingledine
R
R
D000818:Animals; D002712:Chlorides / Q000494:pharmacology*; D004827:Epilepsy / Q000503:physiopathology*; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology*; D011712:Pyramidal Tracts / Q000187:drug effects / Q000502:physiology; D051381:Rats; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D002712:Chlorides; D005680:gamma-Aminobutyric Acid; D011188:Potassium