Cellular metabolism and energy production are fundamental biochemical processes required to maintain life. Metabolic intermediates are widely used as intracellular signalling molecules affecting a host of cellular functions. Since alcohol ingestion results in systemic cellular exposure to ethanol, not only peripherally but also throughout the central nervous system, it is important to consider how ethanol can be utilized as a source of carbon and energy. In neurons, the presence of ethanol preferentially displaces glucose as catabolic input while simultaneously reducing the capacity to utilize glucose once ethanol is exhausted. This shift in energetics is predicted to degrade the capacity of neurons to replenish energy stores upon depolarization. Ethanol has been found to affect neuronal excitability. In one example of a mechanistic link between excitability and ethanol, GIRK2 levels modulate excitability and ethanol increases GIRK2 expression. Overexpression of GIRK2 abrogates both the enhanced firing of glutamatergic neurons and increased respiration rates observed following chronic ethanol treatment. This suggests a novel integration of ethanol metabolism, neuronal excitability and/or firing rates, and ion channel components that may mediate these interactions.
