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1 Physiology, Queen's University, Kingston, ON, Canada
* To whom correspondence should be addressed. E-mail: fergusna{at}post.queensu.ca.
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 OX1R (orexin receptor) and OX2R 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 µM 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 non-selective 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.
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