Inhibition Of GABA-activated Currents By Hypotonic In Rat Trigeminal Ganglion Neurons

Objective: This study was aimed to investigate the modulatory effect of hypotonic on GABA-activated currents (IGABA) in cultured rat trigeminal ganglion (TG) neurons .Method: Whole-cell patch clamp technique. Result: The results were as follows:①The majority of examined neurons (89.2%) were sensitive to GABA (10-1000μM). GABA activated inward currents in a concentration-dependent manner, and IGABA were blocked by bicuculline, a selective antagonist of the GABAA receptor.②When Hypotonic (220, 260,300mOsm) was pre-applied extracellularly, it reduced IGABA significantly. This inhibitory effect was reversible and voltage-independent.The concentration-response curve of GABA was shifted downward by hypotonic without any change of the threshold value.The values of two curves were very close(33.02μM and 29.41μM). Hypotonic decreased the maximal amplitude of IGABA by(31.38±2.13)%.③This inhibitory effect was reversed by ruthenium red, a nonselective TRPV4 receptor antagonist, and was increased by 4ɑ-PDD, a selectively TRPV4 receptor agonist.④Pre-application of BIM, a PKC inhibitor, partially reversed the inhibitory effect of Hypotonic. Conclusion: Hypotonic inhibited IGABA through activation of TRPV4 receptor. The inhibition was mediated partially through activation of PKC system. By inhibiting IGABA, TRPV4 suppressed the signal transmission at central end of primary sensory neuron via enhanced presynaptic inhibition. This is probably one of the mechanisms by which Hypotonic participates in peripheral antinociception.