Orexin-A Depolarizes Nucleus Tractus Solitarius Neurons Through Effects on Nonselective Cationic and K⁺ Conductances

Abstract

The nucleus tractus solitarius (NTS) plays central roles in a number of autonomic functions including cardiovascular control. Orexin (ORX)-A is a 33-amino-acid peptide implicated in the central regulation of energy metabolism, sleep, and the cardiovascular system. Studies demonstrate the presence of ORX-immunoreactive axons and both OX(1)R (orexin receptor) and OX(2)R mRNA within NTS. In this study, whole cell patch-clamp recordings were obtained from NTS neurons in rat medullary slices. Current-clamp studies showed that bath application of various concentrations of ORX-A depolarized 90.7% (78 of 86) of neurons tested while the remaining cells were either unaffected or showed small hyperpolarizations in response to peptide administration. Depolarizing effects were maintained in the presence of 5 microM TTX, and were concentration dependent. Using voltage-clamp techniques, we also identified modulatory actions of ORX-A on specific ion channels. Our results demonstrate that not only does ORX-A inhibit a specific potassium conductance (the sustained K(+) current) in NTS neurons, but it also activates a nonselective cationic conductance (NSCC). These data suggest that ORX-A effects on central cardiovascular control may result from direct actions on NTS neurons and also highlight the ability of this peptide to influence neuronal excitability as a consequence of concurrent modulation of multiple ion channels.

Cerebrospinal fluid orexin in aneurysmal subarachnoid haemorrhage – a pilot study

“…34 At a cellular level, electrophysiological experiments reveal that orexin can modulate synaptic transmission in neurons of the dorsal motor nucleus of the vagus nerve and the nucleus tractus solitarius. 31,35 These findings are particularly pertinent to aneurysmal SAH, which is associated with the development of neurogenic pulmonary oedema, changes in blood pressure, heart rate and myocardial injury, 36 complications which are attributed to abnormal autonomic discharge.…”

Dual Orexin Actions on Dorsal Raphe and Laterodorsal Tegmentum Neurons: Noisy Cation Current Activation and Selective Enhancement of Ca2+ Transients Mediated by L-Type Calcium Channels

“…Hcrt/Orx-activated cation currents have also been reported in area postrema neurons (Yang and Ferguson 2002), nucleus tractus solitarius (Yang and Ferguson 2003), paraventricular hypothalamic neurons (Yang and Ferguson 2002), and locus coruleus (LC) neurons (Murai and Akaike 2005). However, the current reported in those neurons seems different in several respects.…”

Direct and Indirect Inhibition by Catecholamines of Hypocretin/Orexin Neurons

“…These cells have a different function from the LC neurons and may relate more to control of vegetative and homeostatic processes, potentially linking the enteroceptive cells of the gut with the LH. The A2 cells of the nucleus of the solitary tract project to the LH area, and cells of the nucleus of the solitary tract show excitatory responses to hypocretin (Smith et al, 2002;Yang and Ferguson, 2003). Studies combining tract-tracing with immunostaining have shown a very specific innervation of subregions of the hypothalamic paraventricular nucleus by different catecholamine projections (Sawchenko and Swanson, 1982;Cunningham and Sawchenko, 1988).…”