GABA-Induced Seizure-Like Events Caused by Multi-ionic Interactive Dynamics.

Abstract

Experimental evidence showed that an increase in intracellular chloride concentration [Formula: see text] caused by gamma-aminobutyric acid (GABA) input can promote epileptic firing activity, but the actual mechanisms remain elusive. Here in this theoretical work, we show that influx of chloride and concomitant bicarbonate ion [Formula: see text] efflux upon GABA receptor activation can induce epileptic firing activity by transition of GABA from inhibition to excitation. We analyzed the intrinsic property of neuron firing states as a function of [Formula: see text] We found that as [Formula: see text] increases, the system exhibits a saddle-node bifurcation, above which the neuron exhibits a spectrum of intensive firing, periodic bursting interrupted by depolarization block (DB) state, and eventually a stable DB through a Hopf bifurcation. We demonstrate that only GABA stimuli together with [Formula: see text] efflux can switch GABA's effect to excitation which leads to a series of seizure-like events (SLEs). Exposure to a low [Formula: see text] can drive neurons with high concentrations of [Formula: see text] downward to lower levels of [Formula: see text], during which it could also trigger SLEs depending on the exchange rate with the bath. Our analysis and simulation results show how the competition between GABA stimuli-induced accumulation of [Formula: see text] and [Formula: see text] application-induced decrease of [Formula: see text] regulates the neuron firing activity, which helps to understand the fundamental ionic dynamics of SLE.