title: Hippocampal inhibitory neuron activity in the elevated potassium model of epilepsy.
abstract: 1. Whole cell patch-clamp recordings were made from CA1 stratum oriens inhibitory neurons of rat hippocampal slices in vitro to determine their contribution to the epileptiform activity elicited by elevating the extracellular potassium ion concentration ([K+]o) from 3.5 to 8.5 mm. 2. Under current-clamp conditions, spontaneous action potential activity in inhibitory neurons normally occurs in a sustained repetitive firing mode paced by nonsynaptic, intrinsic mechanisms. On elevation of [K+]o to 8.5 mm the pattern of activity is altered such that clusters of action potentials occur interrupted by periods of silence without an appreciable afterhyperpolarization (AHP). In addition, elevation of [K+]o caused a large reduction in the action potential AHP amplitude and duration concomitant with a 20-mV shift in the reversal potential of the AHP. 3. In voltage clamp a small persistent inward current was observed after the introduction of elevated potassium concomitant with an increase in the frequency of spontaneous excitatory post-synaptic currents (EPSCs) in all interneurons studied. After a short period of time (approximately 1 min) temporal summation of synchronously occurring EPSCs contributed a periodic inward current (PIC; 10-40 pA, 0.8 Hz) that persisted for the duration of the [K+]o elevation. Analysis of the charge transfer associated with the PIC suggests that they comprise the temporal summation of approximately 35 EPSCs. This PIC was synchronous with the extracellular field potential recorded from the CA1 pyramidal neuron layer. 4. The PIC was responsible for the clustering of action potential activity because blockade of EPSC activity by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) abolished PICs and reverted action potential activity to single sustained firing, despite the continued application of 8.5 mm [K+]o. Antagonists of N-methyl-D-aspartate receptors were without effect on either the PICs or the action potential activity. 5. Addition of the metabotropic glutamate receptor (mGluR) antagonist (+)-2-methyl-4-carboxyphenylglycine (MCPG) reversibly abolished the PIC without affecting the increase in EPSC frequency. 6. Recordings from CA3 pyramidal neurons in 8.5 mm [K+]o demonstrated that interictal activity occurred at a frequency identical to the PICs observed in interneurons. Interictal activity in CA3 pyramidal neurons was attenuated but never abolished by MCPG, suggesting a role for mGluR receptors in the maintenance of interictal activity in area CA3.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Unit on Cellular and Synaptic Physiology, National Institute of Child Health and Human Development, Bethesda, Maryland 20892.
authors.forename: C J
authors.initials: CJ
authors.lastname: McBain
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D004827:Epilepsy / Q000503:physiopathology*; D006624:Hippocampus / Q000166:cytology / Q000503:physiopathology*; D066298:In Vitro Techniques; D007395:Interneurons / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D015221:Potassium Channels; D018094:Receptors, Metabotropic Glutamate; D005680:gamma-Aminobutyric Acid; D011188:Potassium