Epileptiform activity induced by changes in extracellular potassium in hippocampus

Abstract

Using extra- and intracellular recording techniques, we investigated the induction and frequency modulation of spontaneous epileptiform activity produced by changes in the concentration of extracellular potassium ([K+]o). This paper describes a quantitative relationship between [K+]o and the frequency of spontaneously occurring epileptiform events. Recordings were made from the CA3 subfield of the rat in vitro hippocampal slice preparation. Intracellular microelectrodes were filled with 2 M Cs2SO4 and connected to a 3-kHz, time-share, single-electrode current- and voltage-clamp device. The frequency of spontaneous epileptiform (interictal) discharges was determined from extracellular recordings as a function of [K+]o. Current- and voltage-clamp techniques were used to characterize the intracellular correlate of these epileptiform events. The frequency of bicuculline-induced spontaneous epileptiform discharges was dependent on [K+]o. Below 4 mM [K+]o, spontaneous discharges occurred sporadically in the presence of 10 microM bicuculline. Increasing [K+]o from 5 to 10 mM caused a fivefold increase in the rate of spontaneous discharges. Spontaneous epileptiform discharges also occurred in the absence of bicuculline when [K+]o was increased above 6.5 mM. The rate of these discharges was dependent on [K+]o in much the same way as the discharges induced by bicuculline. For any given [K+]o concentration greater than 6.5 mM, however, the resultant discharge rate was faster than that obtained when bicuculline was present in the bathing solution. Simultaneous intra- and extracellular recordings revealed that the spontaneous high-[K+]o-induced interictal discharge was accompanied by a large depolarization of the membrane potential that appeared similar to the paroxysmal depolarizing shift (PDS) seen with other convulsants. The intracellularly recorded event fulfilled the criteria for a synaptically mediated PDS. The waveform of the PDS was complex and dependent on the membrane potential. When the membrane potential was held at 0 mV, spontaneously occurring hyperpolarizing potentials were noted during the inter-PDS interval. These events were blocked by picrotoxin or bicuculline and were probably spontaneous inhibitory postsynaptic potentials. The complexity of the PDS waveform suggested that more than one synaptic conductance was involved in the generation of the PDS. The mean measured reversal potential of the depolarizing phase was -10.7 mV. Voltage-clamp techniques were used to measure the conductance underlying the depolarizing phase of the high-[K+]o-induced PDS. The mean measured conductance was 51.5 nS, with a reversal potential of -7.9 mV.(ABSTRACT TRUNCATED AT 400 WORDS)

Mechanisms of physiological and epileptic HFO generation

“…Many of them rely on blocking GABA A receptor mediated inhibition with drugs such as picrotoxin, bicuculline or penicillin (Dingledine and Gjerstad, 1979;Schwartzkroin and Prince, 1978). Convulsant treatments which do not block inhibition include 4-aminopyridine (Avoli et al, 1996;D'Antuono et al, 2002;Rutecki et al, 1987), elevated K + (Jiruska et al, 2010a;Rutecki et al, 1985;Traub and Dingledine, 1990) and low Mg 2+ (Anderson et al, 1986;Derchansky et al, 2008). Another acute and realistic model in vivo is brain trauma, which leads to electrographic seizures in the majority of animals (Topolnik et al, 2003).…”

GABAergic synchronization in the limbic system and its role in the generation of epileptiform activity

“…However, the pioneering studies made in Johnston's laboratory with single-electrode voltage-clamp recordings have demonstrated that the amplitude of the interictal responses recorded during application of medium containing 4AP, tetraethylammonium, or elevated [K + ] are characterized by reversal potentials that are more negative than those associated with reversal potentials of paroxysmal depolarization shifts induced by GABA A receptor antagonists (Rutecki et al, 1985(Rutecki et al, , 1987(Rutecki et al, , 1990. Hence, synaptic inhibition is operative in these in vitro models of interictal discharge.…”

Excitatory Actions of Endogenously Released GABA Contribute to Initiation of Ictal Epileptiform Activity in the Developing Hippocampus

“…2 A) (see Figs. 3-7) (Rutecki et al, 1985). This [K ϩ ] o diminishes neuronal Cl Ϫ extrusion by decreasing the driving force for K-Cl cotransport, thereby making the GABA reversal potential more positive (Thompson and Gahwiler, 1989b).…”