Actions of Orphan Opioid on the Membrane Conductances and Synaptic Transmission in Rat Medial Vestibular Nucleus Neurons

ABSTRACT

BACKGROUND: The medial vestibular nucleus (MVN) is involved in the reflex control of the head and eyes, and the recovery of vestibular function after vestibular injuries. This study was performed to investigate the actions of the orphan opioid (nociceptin) on the membrane conductances and synaptic transmission in rat MVN neurons. METHODS: Whole cell patch clamp recordings were carried out in the brainstem slice of neonatal rats. RESULTS: Nociceptin (2 micro M) inhibited the spontaneous discharge in the majority (83%) of MVN neurons. This inhibition was insensitive to the non-specific opioid receptor antagonist naloxone (10 micro M), but was effectively antagonized by the selective opioid receptor-like 1 (ORL1) receptor antagonist, [Nphe1] nociceptin(1-13)NH2 (3 micro M). Nociceptin had no effect on the rate or amplitude of miniature inhibitory postsynaptic currents (mIPSCs). Nociceptin induced an outward current, and which was blocked by [Nphe1] nociceptin(1-13)NH2 in MVN neurons. Outward current reversed at -81 +/- 2 mV, which was close to the K+ equilibrium potential as calculated by the Nernst equation in 6 mM extracellular potassium solution. This indicates that the action of nociceptin involves postsynaptic receptors on the MVN neurons. CONCLUSIONS: These results suggest that nociceptin modulate neuronal excitability by activating a K+ conductance in postsynaptic neurons, not by modulation of synaptic transmission in MVN neurons.