title: Role of intrinsic burst firing, potassium accumulation, and electrical coupling in the elevated potassium model of hippocampal epilepsy.
abstract: Perfusing rat hippocampal slices with high-K+ (7.5 mM) saline induced brief population bursts originating in CA3 at 0.5-1 Hz and spreading synaptically into CA1. In 42% of the slices the brief bursts evoked in CA1 gave way every 0.5-2 s to sustained ictal (or seizure) episode with tonic and clonic components. Paired intra- and extracellular recordings in the CA1 pyramidal layer were used to characterize the synaptic and nonsynaptic mechanisms generating the brief and sustained epileptiform events. The interictal, tonic, or clonic primary burst response in CA1 comprised a spindle-shaped, tight cluster (170-180 Hz) of five to seven population spikes. Bursts evoked between sequential seizures (interictal bursts) were initially small and progressively increased in size. Concurrently, basal extracellular K+ concentration ([K+]o] increased from 6.5 to 7.5 mM. The tonic event emanated from a large primary burst and comprised prolonged (> 1 s), self-sustained afterdischarge, associated with a rise in [K+]o to 12 mM. Bursts generated during the subsequent [K+]o decline (clonic bursts) also were large and followed by some afterdischarge. They became small during [K+]o undershoot to 6.5 mM. Intrinsically burst firing pyramidal cells (PCs) were recruited before or at the very onset of the primary population burst and fired repetitively during its course. Nonbursters were recruited > or = 10 ms after the beginning of the primary burst and fired, on average, only one spike. The PCs depolarized during the primary burst and subsequent afterdischarge. The primary depolarizing shift was larger in bursters than in nonbursters. Both bursters and nonbursters fired repetitively, albeit intermittently, during tonic and clonic afterdischarge. Throughout the interictal-ictal cycle intracellular spikes were time-locked to population spikes, indicating that PCs fire in tight synchrony. Differential recording of transmembrane potentials unmasked rapid (4-7 ms) transmembrane depolarizing potentials of up to 10 mV, coincident with population spikes. We conclude that in the high-K+ model of hippocampal epilepsy, the local generation of population bursts in CA1 is led by intrinsic bursters, which recruit and synchronize other PCs by synaptic, electrical, and K(+)-mediated excitatory interactions. The cycling between interictal, tonic, and clonic events appears to result from feedback interactions between neuronal discharge and [K+]o.
authors.affiliation: PharmaBiotech, Institute of Physiology, Aarhus University, Denmark.
authors.forename: M S
authors.initials: MS
authors.lastname: Jensen
authors.forename: Y
authors.initials: Y
authors.lastname: Yaari
mesh_terms: D000818:Animals; D004558:Electric Stimulation; D004594:Electrophysiology; D004827:Epilepsy / Q000378:metabolism / Q000503:physiopathology*; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000502:physiology; D008839:Microelectrodes; D011188:Potassium / Q000378:metabolism / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011999:Recruitment, Neurophysiological; D013569:Synapses / Q000502:physiology
chemical_list: D011188:Potassium