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J Neurophysiol (April 1, 2003). 10.1152/jn.01088.2002
Submitted on Submitted 4 December 2002; accepted in final form 20 December 2002
Department of Physiology, Queen's University, Kingston, Ontario K7L 3N6, Canada
Yang, Bo and
Alastair V. Ferguson.
Orexin-A Depolarizes Nucleus Tractus Solitarius Neurons Through
Effects on Nonselective Cationic and K+ Conductances. J. Neurophysiol. 89: 2167-2175, 2003. 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 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.
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