GABAA receptors mediate motoneuron tonic inhibition in the turtle spinal cord

Abstract

GABA(A) receptors mediating tonic inhibitory currents are present in neurons from hippocampus, cerebellum, sensory cortex and thalamus. These receptors located at peri- and extra-synaptic sites are constituted mainly by α(4/6) and α(5) subunits which confer them high affinity for GABA and low desensitization. Immunohistochemical and in vitro hybridization studies have shown the expression of these subunits, while functional studies have reported the presence of GABAergic tonic currents in spinal dorsal horn neurons. However, the presence of this inhibitory current has not been documented in motoneurons. In addition, we previously reported that the monosynaptic reflex is facilitated by furosemide, an antagonist of the α(4/6) GABA(A) receptors, without affecting the dorsal root potential, which suggests the presence of a GABAergic tonic inhibitory current in motoneurons. The aim of this work was to investigate the presence of high affinity GABA(A) receptors in motoneurons. By intracellular recordings made with sharp electrodes and the whole-cell patch clamp recording technique we show here that the membrane input resistance and the monosynaptic excitatory post-synaptic potential (EPSPs) are significantly increased by bicuculline. Likewise, the depression of the EPSPs and the input membrane resistance normally induced by muscimol was partially reverted by 20 μM bicuculline and abolished when the concentration of the antagonist was raised to 100 μM. Last, bicuculline at low concentration did not affect the holding current as occur with the high concentration that block the tonic inhibitory GABAergic current. Together these results suggest that the excitability in motoneurons may be tonically inhibited by high affinity GABA(A) receptors.