Ethanol Affects Network Activity in Cultured Rat Hippocampus: Mediation by Potassium Channels

Abstract

The effects of ethanol on neuronal network activity were studied in dissociated cultures of rat hippocampus. Exposure to low (0.25–0.5%) ethanol concentrations caused an increase in synchronized network spikes, and a decrease in the duration of individual spikes. Ethanol also caused an increase in rate of miniature spontaneous excitatory postsynaptic currents. Higher concentrations of ethanol eliminated network spikes. These effects were reversible upon wash. The effects of the high, but not the low ethanol were blocked by the GABA antagonist bicuculline. The enhancing action of low ethanol was blocked by apamin, an SK potassium channel antagonist, and mimicked by 1-EBIO, an SK channel opener. It is proposed that in cultured hippocampal networks low concentration of ethanol is associated with SK channel activity, rather than the GABAergic receptor.

Chronic exposure to alcohol alters network activity and morphology of cultured hippocampal neurons

“…In the initial series of experiments we replicated and extended our previous observations on the effects of ethanol on network activity in cultured hippocampal neurons (Korkotian et al, 2013). Consecutive exposure of the cultures to concentrations of ethanol from 0.5% to 1% caused initially an increase in the rate of network bursts.…”

Developmental Ethanol Exposure Leads to Long-Term Deficits in Attention and Its Underlying Prefrontal Circuitry

“…This decreased firing frequency may result from the larger AHP amplitudes measured in neurons from mice in the ethanol group, which in turn are influenced by BK and SK calcium-activated potassium channels (Faber and Sah, 2003; Pedarzani and Stocker, 2008). Although acute ethanol exposure decreases neuronal excitability through BK channels (Martin et al, 2004; Dopico et al, 2014) and increases neuronal excitability through SK channels (Brodie et al, 1999; Korkotian et al, 2013), long-term consequences of developmental ethanol exposure on these channels and their specific roles in mPFC layer VI neuron excitability remain to be determined.…”

Alcohol and the Brain: Neuronal Molecular Targets, Synapses, and Circuits

“…Ethanol inhibits SK2 channel currents in a heterologous expression system (Dreixler et al, 2000), but there is no evidence of direct ethanol interactions with this channel. However, a number of studies indicate that chronic ethanol exposure and withdrawal reduce SK channel function in the ventral tegmental area (VTA) dopamine, hippocampal CA1 (Figure 3A), and cortical neurons (reviewed in Mulholland et al, 2009, 2011; Nimitvilai et al, 2016a; Korkotian et al, 2013). Furthermore, decreased SK channel expression and function were observed in the nucleus accumbens (NAc) core after ethanol self-administration.…”