LAUSR

The vestibular system is modulated by various neuromodulators including opioid peptides. The current study was conducted to determine whether activation of nociceptin/orphanin FQ peptide (NOP) receptors modulates voltage-gated calcium currents and action potential discharge of rat vestibular afferent neurons. We performed whole cell patch clamp recordings on cultured vestibular afferent neurons from P7 - P10 Long-Evans rats. Application of nociceptin/orphanin FQ (N/OFQ), a 17-amino acid neuropeptide which is the endogenous ligand for NOP receptor, inhibits the high-voltage activated (HVA)component of the calcium current in a concentration-dependent manner with a half inhibitory concentration of 26 nM. Said inhibitory action on the calcium current is voltage-dependent, which was made clear by the fact that it was reverted in 80 % by a depolarizing pre-pulse. Furthermore, the effect of N/OFQ was blocked by application of the specific NOP-antagonist UFP101, by pre-incubation with G-protein blocker pertussis toxin, and by co-application of the specific N-type calcium-current blocker ω-conotoxin -MVIIA. N/OFQ application causes an increase in the duration and maximum rate of repolarization of action potentials. It also decreases repetitive discharge, and discharge elicited by sinusoidal stimulation. These results show that in vestibular afferents, NOP receptor activation inhibits N-type calcium current by activating G proteins, mostly through the Gbg subunit. This suggests that NOP activation produces a pre-synaptic modulation of primary vestibular afferent neurons output into the vestibular nuclei, thus taking part in the integration and gain setting of vestibular information in second order vestibular nucleus neurons.