Orexin-A depolarizes dissociated rat area postrema neurons through activation of a nonselective cationic conductance.
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(Omega), 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 10(-11) 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.
Yang
Bo
B
Department of Physiology, Queen's University, Kingston, Ontario, Canada K7L 3N6.
Ferguson
Alastair V
AV
D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology*; D002412:Cations / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D020546:Fourth Ventricle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000145:classification / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D009479:Neuropeptides / Q000494:pharmacology*; D000068797:Orexins; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D002352:Carrier Proteins; D002412:Cations; D047908:Intracellular Signaling Peptides and Proteins; D007473:Ion Channels; D009479:Neuropeptides; D000068797:Orexins; D011188:Potassium