Abstract
Locus coeruleus (LC) nucleus and mesencephalic trigeminal nucleus (MesV) are innervated by orexin-like immunoreactive axons, and neurons in these nuclei express orexin receptors (OXRs), OX1R or OX2R, respectively (Greco, M.A. et al., 2001). We analyzed effects of ORX-A/B on dissociated LC or MesV neurons by using whole-cell patch clamp techniques. In current-clamp mode about 50% of both LC and MesV neurons were depolarized by application of 10−7 M ORX-A (3-10 mV), while ORX-B (10−7 M) depolarized about 40% LC or MesV neurons (3-5 mV). LC neurons normally showed a rapid increase in a firing frequency (from 0.2 Hz to 1.0 Hz) and returned to control levels soon after removal of ORX-A/B. These effects were maintained in the presence of TTX, CNQX, AP5 or bicucullin. It indicates direct effect of ORX-A/B on these neurons. MesV neurons rarely fired spontaneously, even either in a current-applied depolarizing condition, but showed the membrane depolarization and the firing of action potentials in an orexin application. In voltage clamp analysis, we demonstrated that ORX-A/B enhanced a non-selective cationic conductance (NSCC) and inhibited conductance of the sustained K+ current (IK). The activation of an NSCC and inhibition of IK mediate the depolarization and broadening of the action potentials caused by ORX-A/B in both LC and MesV neurons. [Jpn J Physiol 54 Suppl:S139 (2004)]
