Back to Search
Start Over
Effects of a TRPV1 agonist capsaicin on respiratory rhythm generation in brainstem-spinal cord preparation from newborn rats.
- Source :
-
Pflugers Archiv : European journal of physiology [Pflugers Arch] 2017 Feb; Vol. 469 (2), pp. 327-338. Date of Electronic Publication: 2016 Nov 29. - Publication Year :
- 2017
-
Abstract
- The heat-sensitive transient receptor potential vanilloid 1 (TRPV1) channels are expressed in the peripheral and central nervous systems. However, there is no report on how the activation of TRPV1 causes the modulation of neuronal activity in the medullary respiratory center. We examined effects of capsaicin, a specific agonist of TRPV1 channels, on respiratory rhythm generation in brainstem-spinal cord preparation from newborn rats. Capsaicin induced a biphasic response in the respiratory rhythm (a transient decrease followed by an increase in the C4 rate). The second-phase excitatory effect (but not the initial inhibitory effect) in the biphasic response was partly blocked by capsazepine or AMG9810 (TRPV1 antagonists). Capsaicin caused strong desensitization. After its washout, the strength of C4 burst inspiratory activity was augmented once per four to five respiratory cycles. The preinspiratory and inspiratory neurons showed tonic firings due to membrane depolarization during the initial inhibitory phase. In the presence of TTX, capsaicin increased the fluctuation of the membrane potential of the CO <subscript>2</subscript> -sensitive preinspiratory neurons in the parafacial respiratory group (pFRG), accompanied by slight depolarization. The C4 inspiratory activity did not stop, even 60-90 min after the application of 50/100 μM capsaicin. Voltage-sensitive dye imaging demonstrated that the spatiotemporal pattern of the respiratory rhythm generating networks after application of capsaicin (50 μM, 70-90 min) was highly similar to the control. A histochemical analysis using TRPV1 channel protein antibodies and mRNA demonstrated that the TRPV1 channel-positive cells were widely distributed in the reticular formation of the medulla, including the pFRG. Our results showed that the application of capsaicin in the medulla has various influences on the respiratory center: transient inhibitory and subsequent excitatory effects on the respiratory rhythm and periodical augmentation of the inspiratory burst pattern. The effects of capsaicin were partially blocked by TRPV1 antagonists but could be also induced at least partially via the non-specific action. Our results also suggested a minor contribution of the TRPV1 channels to central chemoreception.
- Subjects :
- Acrylamides pharmacology
Animals
Animals, Newborn
Bridged Bicyclo Compounds, Heterocyclic pharmacology
Capsaicin analogs & derivatives
Medulla Oblongata drug effects
Membrane Potentials drug effects
Neurons drug effects
Rats
Rats, Wistar
TRPV Cation Channels antagonists & inhibitors
Voltage-Sensitive Dye Imaging methods
Brain Stem drug effects
Capsaicin pharmacology
Respiration drug effects
Spinal Cord drug effects
TRPV Cation Channels agonists
Subjects
Details
- Language :
- English
- ISSN :
- 1432-2013
- Volume :
- 469
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Pflugers Archiv : European journal of physiology
- Publication Type :
- Academic Journal
- Accession number :
- 27900462
- Full Text :
- https://doi.org/10.1007/s00424-016-1912-8