Effects of barium on stimulus‐induced rises of [K⁺]_o in human epileptic non‐sclerotic and sclerotic hippocampal area CA1

Abstract

In the hippocampus of patients with therapy-refractory temporal lobe epilepsy, glial cells of area CA1 might be less able to take up potassium ions via barium-sensitive inwardly rectifying and voltage-independent potassium channels. Using ion-selective microelectrodes we investigated the effects of barium on rises in [K+]o induced by repetitive alvear stimulation in slices from surgically removed hippocampi with and without Ammon's horn sclerosis (AHS and non-AHS). In non-AHS tissue, barium augmented rises in [K+]o by 147% and prolonged the half time of recovery by 90%. The barium effect was reversible, concentration dependent, and persisted in the presence of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), N-methyl-D-aspartate (NMDA) and gamma-aminobutyric acid [GABA(A)] receptor antagonists. In AHS tissue, barium caused a decrease in the baseline level of [K+]o. In contrast to non-AHS slices, in AHS slices with intact synaptic transmission, barium had no effect on the stimulus-induced rises of [K+]o, and the half time of recovery from the rise was less prolonged (by 57%). Under conditions of blocked synaptic transmission, barium augmented stimulus-induced rises in [K+]o, but only by 40%. In both tissues, barium significantly reduced negative slow-field potentials following repetitive stimulation but did not alter the mean population spike amplitude. The findings suggest a significant contribution of glial barium-sensitive K+-channels to K+-buffering in non-AHS tissue and an impairment of glial barium-sensitive K+-uptake in AHS tissue.

Astrocyte dysfunction in temporal lobe epilepsy: K+ channels and gap junction coupling

“…In line with this assumption was also the observation of impaired K 1 buffering and prolonged seizure duration in AQP4 knockout mice (Binder et al, 2006) although spatial K 1 redistribution was more efficient in these mice, probably due to enhanced astrocyte gap junction coupling and volume regulation (Benfenati et al, 2011;Strohschein et al, 2011). However, more recent data from astrocytes and retinal M€ uller cells suggested that Kir4.1 channel function is independent of AQP4 expression (Ruiz-Ederra et al, 2007;Zhang and Verkman, 2008 , this finding suggested impaired function of these channels in the sclerotic tissue (Jauch et al, 2002;Kivi et al, 2000). The hypothesis could be confirmed with patch-clamp analyses demonstrating downregulation of Kir currents in the CA1 region of HS patients (Bordey and Sontheimer, 1998;Hinterkeuser et al, 2000).…”

Infraslow oscillations modulate excitability and interictal epileptic activity in the human cortex during sleep

“…In addition, multiple lines of evidence have pointed to a generation of large-scale, slow electric signals by nonneuronal sources, such as the glial cells (17,(36)(37)(38) and the blood-brain barrier (see refs. 14 and 39 and references therein).…”

Prolonged seizures recruit caudal subventricular zone glial progenitors into the injured hippocampus

“…Although they may contribute to repair, recent work suggests that immature astrocytes may promote an epileptic phenotype. Two groups have identified astrocytes with immature features in the sclerotic CA1 region of human hippocampi resected to treat intractable mTLE but not in nonsclerotic hippocampi (Hinterkeuser et al, 2000;Kivi et al, 2000). These glia possess barium-insensitive potassium channels typical of immature glia.…”