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The Journal of Neuroscience, August 1, 2002, 22(15):6303-6308
BRIEF COMMUNICATION
Orexin-A Depolarizes Dissociated Rat Area Postrema Neurons
through Activation of a Nonselective Cationic Conductance
Bo
Yang and
Alastair V.
Ferguson
Department of Physiology, Queen's University, Kingston, Ontario,
Canada K7L 3N6
The area postrema (AP) is involved in the regulation of body fluid
balance, feeding behavior, and cardiovascular function. Orexin (ORX)-A
is a 33 aa peptide that regulates energy metabolism and sympathetic and
cardiovascular actions. ORX immunoreactive axons and their varicose
terminals have been found in AP. In this study, whole-cell, current- or
voltage-clamp recordings were obtained from 108 dissociated rat AP
neurons. The mean resting membrane potential of these neurons
(n = 48) was  59.24 ± 0.87 mV, the mean
input resistance was 3.57 ± 0.22 G , and the action potential amplitude of these cells was always >90 mV. Current-clamp studies showed bath application of ORX-A depolarized the majority of AP neurons
tested (68.8%; 33 of 48), whereas small proportions of cells were
either hyperpolarized (16.7%; 8 of 48) or unaffected (14.6%; 7 of
48). These depolarizing effects were found to be concentration
dependent from 10 8 to 1011
M. We then examined the contributions of specific ionic
conductances to the ORX-A-induced excitation of AP neurons through
whole-cell, voltage-clamp studies. Our results demonstrate that in
contrast to previous studies on other neuronal populations, ORX-A did
not affect net whole-cell potassium currents in AP neurons. Slow
depolarizing voltage ramps, however, revealed that ORX-A enhanced a
nonselective cationic conductance in AP neurons, effects which would
explain the depolarizing effects of the peptide. These data demonstrate that AP neurons are directly influenced by ORX-A and suggest that ORX-A
may exert its effects on the central control of feeding behavior and
cardiovascular function through direct actions in AP.
Key words:
area postrema; orexin-A; patch-clamp; nonselective
cationic conductance; electrophysiology; central control of feeding
behavior; cardiovascular function
Copyright © 2002 Society for Neuroscience 0270-6474/02/22156303-06$05.00/0
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