Nerve growth factor sensitizes adult sympathetic neurons to the proinflammatory peptide bradykinin

Levels of nerve growth factor (NGF) are elevated in inflamed tissues. In sensory neurons, increases in NGF augment neuronal sensitivity (sensitization) to noxious stimuli. Here, we hypothesized that NGF also sensitizes sympathetic neurons to proinflammatory stimuli. We cultured superior cervical gan...

Celý popis

Uloženo v:

Podrobná bibliografie
Vydáno v:	The Journal of neuroscience Ročník 34; číslo 36; s. 11959
Hlavní autoři:	Vivas, Oscar, Kruse, Martin, Hille, Bertil
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States 03.09.2014
Témata:	Action Potentials Animals Bradykinin - pharmacology Calcium Channel Blockers - pharmacology Calcium Channels - metabolism Calcium Signaling Cells, Cultured Inflammation Mediators - pharmacology Large-Conductance Calcium-Activated Potassium Channels - antagonists & inhibitors Large-Conductance Calcium-Activated Potassium Channels - metabolism Male Nerve Growth Factor - pharmacology Neurons - drug effects Neurons - metabolism Neurons - physiology Nifedipine - pharmacology Paxillin - pharmacology Peptides - pharmacology Phosphatidylinositol 4,5-Diphosphate - metabolism Potassium Channel Blockers - pharmacology Rats Rats, Sprague-Dawley Receptor, trkA - metabolism Superior Cervical Ganglion - cytology Superior Cervical Ganglion - drug effects Superior Cervical Ganglion - metabolism Superior Cervical Ganglion - physiology BK channel nifedipine-sensitive calcium channel Maxi-K channel superior cervical ganglion neurons slo1 channel M-current
ISSN:	1529-2401, 1529-2401
On-line přístup:	Zjistit podrobnosti o přístupu
Tagy:	Přidat tag Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!

Popis
Shrnutí:	Levels of nerve growth factor (NGF) are elevated in inflamed tissues. In sensory neurons, increases in NGF augment neuronal sensitivity (sensitization) to noxious stimuli. Here, we hypothesized that NGF also sensitizes sympathetic neurons to proinflammatory stimuli. We cultured superior cervical ganglion (SCG) neurons from adult male Sprague Dawley rats with or without added NGF and compared their responsiveness to bradykinin, a proinflammatory peptide. The NGF-cultured neurons exhibited significant depolarization, bursts of action potentials, and Ca(2+) elevations after bradykinin application, whereas neurons cultured without NGF showed only slight changes in membrane potential and cytoplasmic Ca(2+) levels. The NGF effect, which requires trkA receptors, takes hours to develop and days to reverse. We addressed the ionic mechanisms underlying this sensitization. NGF did not alter bradykinin-induced M-current inhibition or phosphatidylinositol 4,5-bisphosphate hydrolysis. Maxi-K channel-mediated current evoked by depolarizations was reduced by 50% by culturing neurons in NGF. Application of iberiotoxin or paxilline, blockers of Maxi-K channels, mimicked NGF treatment and sensitized neurons to bradykinin application. A calcium channel blocker also mimicked NGF treatment. We found that NGF reduces Maxi-K channel opening by decreasing the activity of nifedipine-sensitive calcium channels. In conclusion, culture in NGF reduces the activity of L-type calcium channels, and secondarily, the calcium-sensitive activity of Maxi-K channels, rendering sympathetic neurons electrically hyper-responsive to bradykinin.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1529-2401 1529-2401
DOI:	10.1523/JNEUROSCI.1536-14.2014