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dc.contributor.authorIngves, Matthew
dc.contributor.otherQueen's University (Kingston, Ont.). Theses (Queen's University (Kingston, Ont.))en
dc.date2009-08-18 11:18:05.977en
dc.date.accessioned2009-08-20T20:23:45Z
dc.date.available2009-08-20T20:23:45Z
dc.date.issued2009-08-20T20:23:45Z
dc.identifier.urihttp://hdl.handle.net/1974/5068
dc.descriptionThesis (Master, Physiology) -- Queen's University, 2009-08-18 11:18:05.977en
dc.description.abstractLittle is known regarding the neurophysiological mechanisms by which the neuropeptide prokineticin 2 (PK2) regulates circadian rhythms. Using whole-cell electrophysiology, we have investigated a potential role for regulation of neuronal excitability by PK2 on neurons of the area postrema (AP), a medullary structure known to influence autonomic processes in the central nervous system. In current-clamp recordings, focal application of 1µM PK2 reversibly influenced the excitability of the majority of dissociated AP cells tested, producing both depolarizations (38%) and hyperpolarizations (28%) in a concentration-dependent manner. Slow voltage ramps and ion substitution experiments revealed a PK2-induced Cl- current was responsible for membrane depolarization, while hyperpolarizations were the result of inhibition of an inwardly rectifying non-selective cation current. In contrast to these differential effects on membrane potential, nearly all neurons that displayed spontaneous activity responded to PK2 with a decrease in spike frequency. These observations are in accordance with voltage-clamp experiments showing that PK2 caused a leftward shift in Na+ channel activation and inactivation gating. Lastly, using post hoc single cell RT-PCR technology, we have shown that 7 out of 10 AP neurons depolarized by PK2 were enkephalin-expressing cells. The observed actions on enkephalin neurons indicate PK2 may have specific inhibitory actions on this population of neurons in the AP acting to reduce their sensitivity to incoming signals. These data suggest that PK2 regulates the level of AP neuronal excitability and may impart a circadian influence on AP autonomic control.en
dc.format.extent1603188 bytes
dc.format.mimetypeapplication/pdf
dc.languageenen
dc.language.isoenen
dc.relation.ispartofseriesCanadian thesesen
dc.rightsThis publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.en
dc.subjectEnkephalinen
dc.subjectCircumventricularen
dc.subjectPatch Clampen
dc.subjectSingle Cell RT-PCRen
dc.subjectNeuropeptideen
dc.subjectAction Potentialen
dc.titleThe Area Postrema: A Potential Site for Circadian Regulation by Prokineticin 2en
dc.typethesisen
dc.description.degreeMasteren
dc.contributor.supervisorFerguson, Alastair V.en
dc.contributor.departmentPhysiologyen


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