Taurine potentiates the anticonvulsive effect of the GABAA agonist muscimol and pentobarbital in the immature mouse hippocampus

Summary

Objective

The high incidence of epileptic seizures in neonates and their frequent refractoriness to pharmacologic therapies require identification of new therapeutical options. Therefore, we investigated whether the modulatory effect of taurine on γ‐aminobutyric acid (GABA)_A receptors can enhance the anticonvulsive potential of the GABA_A receptor agonist muscimol and of the barbiturate pentobarbital.

Methods

We performed field potential recordings in in toto hippocampus preparations of immature (postnatal days 4‐7) C57Bl/6 mouse pups. Spontaneous epileptiform activity was induced by the continuous presence of the potassium channel blocker 4‐aminopyridine and the glycinergic antagonist strychnine in Mg²⁺‐free solutions.

Results

Bath application of 0.1 μmol/L muscimol increases the occurrence of recurrent epileptiform discharges, whereas they are significantly attenuated in a dose‐dependent manner by muscimol in concentrations between 0.5 and 5 μmol/L. Taurine at concentrations between 0.1 and 0.5 mmol/L induces a proconvulsive effect, but upon coapplication, it significantly augments the anticonvulsive effect of moderate muscimol doses (0.5‐1 μmol/L). In addition, the anticonvulsive effect of 100 and 200 μmol/L pentobarbital is increased significantly in the presence of 0.5 μmol/L taurine.

Significance

These observations demonstrate that taurine can indeed enhance the anticonvulsive effects of muscimol and pentobarbital, suggesting that taurine may act as a positive modulator on GABA_A receptors. Thus, interfering with the modulatory taurine binding site of GABA_A receptors or the interstitial taurine concentration may provide new therapeutical options for anticonvulsive therapies in neonates.

http://bit.ly/2Wk17wY