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bioRxiv · 10.64898/2026.01.29.702224

Bicarbonate Efflux induces GABAergic Excitation and Seizures through pH Regulation

Liu, Z.·Li, Y.
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Abstract

GABAergic signaling can paradoxically excite neurons and initiate seizures, but the underlying mechanisms remain unclear. We developed a computational model integrating pH regulation into neural dynamics to investigate GABAergic excitation. Our results show that GABA-induced bicarbonate efflux causes intracellular acidification and charge accumulation, which enhances neuronal excitability and can trigger seizure-like discharges through bifurcations in the neurodynamic system. Furthermore, we demonstrate that active pH-regulating transporters effectively counteract GABA-induced acidification to maintain neural stability. This work elucidates a novel pH-regulating mechanism for excitatory GABA responses, explaining how impaired pH regulation or excessive GABA stimulation may predispose neurons to seizures and suggesting new therapeutic targets for epilepsy.

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Liu, Z., Li, Y.. 2026-02-02. Bicarbonate Efflux induces GABAergic Excitation and Seizures through pH Regulation. https://doi.org/10.64898/2026.01.29.702224

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