A neglected GABAergic astrocyte: Calcium dynamics and involvement in seizure activity

Gamma-aminobutyric acid (GABA) contributes substantially to neurocognitive function as an important inhibitory neurotransmitter in the human cerebral cortex. However, the pathophysiology of disorders such as epilepsy are not well understood, since GABA agonists are not quite effective in treating epilepsy. Knowledge of the mechanism of action of GABA would contribute to review previously proposed anti-epileptic processes by GABA agonists. In this study based on recent experiments on GABAergic astrocytes, we developed a modified GABAergic astrocyte model, and successfully simulated a long-lasting Ca²⁺ oscillation in astrocytes after 0.5-s stimulation of GABAergic transmission. We then incorporated this GABAergic astrocyte model into a classical Ullah-Schiff seizure model and surprisingly found that this GABAergic astrocyte model functions to hinder the anti-epileptic action of GABA agonists, thereby explaining their low efficiency in previous experiments. These results also update our knowledge of the mechanism of action of GABA and the effects of astrocytes on physiological and pathological functions of the brain.