title: Prokineticin 2 modulates the excitability of area postrema neurons in vitro in the rat.
abstract: Despite recent evidence describing prokineticin 2 (PK2)-producing neurons and receptors in the dorsomedial medulla, little is known regarding the potential mechanisms by which this circadian neuropeptide acts in the medulla to influence autonomic function. Using whole cell electrophysiology, we have investigated a potential role for PK2 in the regulation of excitability in 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 1 microM PK2 reversibly influenced the excitability of the majority of dissociated AP cells tested, producing depolarizations (38%) and hyperpolarizations (28%) in a concentration-dependent manner. Slow voltage ramps and ion-substitution experiments revealed that a PK2-induced Cl(-) current was responsible for membrane depolarization, whereas hyperpolarizations were the result of inhibition of a nonselective 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 of 10 enkephalin-expressing AP neurons were depolarized by PK2 indicating that PK2 may have specific inhibitory actions on this population of neurons in the AP to reduce their sensitivity to homeostatic signals. These data suggest that the level of AP neuronal excitability may be regulated by PK2, ultimately affecting AP autonomic control.
authors.affiliation: Department of Physiology, Queen's University, Kingston, ON, Canada K7L 3N6.
authors.forename: Matthew V
authors.initials: MV
authors.lastname: Ingves
authors.forename: Alastair V
authors.initials: AV
authors.lastname: Ferguson
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D031608:Area Postrema / Q000166:cytology* / Q000502:physiology*; D001341:Autonomic Nervous System / Q000166:cytology / Q000502:physiology; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology; D004745:Enkephalins / Q000378:metabolism; D005768:Gastrointestinal Hormones / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009479:Neuropeptides / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015222:Sodium Channels / Q000502:physiology
chemical_list: D002712:Chlorides; D004745:Enkephalins; D005768:Gastrointestinal Hormones; D009479:Neuropeptides; D015222:Sodium Channels; C513686:prokineticin 2, rat