Persistent sodium conductance contributes to orexin-A-mediated modulation of membrane excitability in neonatal rat mesencephalic V neurons

Orexins are multifunctional hypothalamic neuropeptides that participate in the stimulation of feeding behavior and energy expenditure. However, little is known about their neuromodulatory effects in lower brainstem effector regions, including in the trigeminal neuronal system. The aim of this study was to examine the effects of orexin-A (Ox-A) on the membrane properties of mesencephalic trigeminal (Mes V) neurons that are critically involved in the generation and control of rhythmical oral motor activities. Whole-cell patch clamp recordings were obtained from Mes V neurons in coronal brain slices prepared from Sprague-Dawley rats (postnatal day 12-17). Bath application of Ox-A (100 nM) shortened the duration of the after-hyperpolarization following the action potential, while the interspike frequency of firings during repetitive discharge increased, together with a shift in the frequency-current relationship toward the left. In addition, Ox-A amplified the resonance at the depolarized membrane potential, accompanied with an increase in both Q-value and resonant frequency. A further voltage-clamp experiment demonstrated that Ox-A increased the peak current density of the persistent sodium current (I_NaP) and shifted its activation curve to the hyperpolarization direction. These results suggested that Ox-A may increase Mes V neuronal excitability by enhancing I_NaP, possibly sharing a common mechanism with another orexigenic hypothalamic neuropeptide, neuropeptide Y.