| Prokineticin 2 influences subfornical organ neurons through regulation of MAP kinase and the modulation of sodium channels. | |
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MedLine Citation:
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PMID: 18614763 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Prokineticin 2 (PK2) is a neuropeptide that acts as a signaling molecule regulating circadian rhythms in mammals. We have previously reported PK2 actions on subfornical organ (SFO) neurons, identifying this circumventricular organ as a target at which PK2 acts to influence autonomic control (Cottrell GT, and Ferguson AV. J. Neurosci. 24: 2375-2379, 2004). In this study, we have examined the cellular mechanisms by which PK2 increases the excitability of SFO neurons. Whole cell patch recordings from dissociated rat SFO neurons demonstrated that the mitogen-activated protein (MAP) kinase inhibitor PD-98059 prevented PK2-induced depolarization and decreases in delayed rectifier K(+) current. PK2 also increased intracellular Ca(2+) concentration ([Ca(2+)](i)) in 39% of dissociated SFO neurons (mean increase = 20.8 +/- 5.5%), effects that were maintained in the presence of thapsigargin but abolished by both nifedipine, or the absence of extracellular Ca(2+), suggesting that PK2-induced [Ca(2+)](i) transients resulted from Ca(2+) entry through voltage-gated Ca(2+) channels. Voltage-clamp recordings showed that PK2 was without effects on Ca(2+) currents evoked by voltage ramps, suggesting that PK2-induced Ca(2+) influx was secondary to PK2-induced increases in action potential frequency, an hypothesis supported by data showing that tetrodotoxin abolished effects of PK2 on [Ca(2+)](i). These observations suggested PK2 modulation of voltage-gated Na(+) currents, a possibility confirmed by voltage-clamp experiments showing that PK2 increased the amplitude of both transient and persistent Na(+) currents in 29% of SFO neurons (by 34 and 38%, respectively). These data indicate that PK2 influences SFO neurons through the activation of a MAP kinase cascade, which, in turn, modulates Na(+) and K(+) conductances. |
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Authors:
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Mark Fry; G Trevor Cottrell; Alastair V Ferguson |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-07-09 |
Journal Detail:
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Title: American journal of physiology. Regulatory, integrative and comparative physiology Volume: 295 ISSN: 0363-6119 ISO Abbreviation: Am. J. Physiol. Regul. Integr. Comp. Physiol. Publication Date: 2008 Sep |
Date Detail:
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Created Date: 2008-09-08 Completed Date: 2008-10-17 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 100901230 Medline TA: Am J Physiol Regul Integr Comp Physiol Country: United States |
Other Details:
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Languages: eng Pagination: R848-56 Citation Subset: IM |
Affiliation:
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Dept. of Physiology, Queen's Univ., Botterell Hall, 4floor, Kingston, ON, Canada K7L 3N6. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Autonomic Nervous System / physiology Calcium / metabolism Calcium Channels / physiology Calcium Channels, L-Type / physiology Gastrointestinal Hormones / physiology* Ion Channel Gating / physiology Male Mitogen-Activated Protein Kinases / metabolism* Neurons / enzymology* Neuropeptides / physiology* Patch-Clamp Techniques Potassium / metabolism Rats Rats, Sprague-Dawley Sodium / metabolism Sodium Channels / physiology* Subfornical Organ / cytology, physiology* |
| Chemical | |
Reg. No./Substance:
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0/Calcium Channels; 0/Calcium Channels, L-Type; 0/Gastrointestinal Hormones; 0/Neuropeptides; 0/Sodium Channels; 0/prokineticin 2, rat; 7440-09-7/Potassium; 7440-23-5/Sodium; 7440-70-2/Calcium; EC 2.7.11.24/Mitogen-Activated Protein Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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