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Modulation of voltage-gated Ca2+ channels by G protein-coupled receptors in celiac-mesenteric ganglion neurons of septic rats.
- Source :
-
PloS one [PLoS One] 2015 May 27; Vol. 10 (5), pp. e0125566. Date of Electronic Publication: 2015 May 27 (Print Publication: 2015). - Publication Year :
- 2015
-
Abstract
- Septic shock, the most severe complication associated with sepsis, is manifested by tissue hypoperfusion due, in part, to cardiovascular and autonomic dysfunction. In many cases, the splanchnic circulation becomes vasoplegic. The celiac-superior mesenteric ganglion (CSMG) sympathetic neurons provide the main autonomic input to these vessels. We used the cecal ligation puncture (CLP) model, which closely mimics the hemodynamic and metabolic disturbances observed in septic patients, to examine the properties and modulation of Ca2+ channels by G protein-coupled receptors in acutely dissociated rat CSMG neurons. Voltage-clamp studies 48 hr post-sepsis revealed that the Ca2+ current density in CMSG neurons from septic rats was significantly lower than those isolated from sham control rats. This reduction coincided with a significant increase in membrane surface area and a negligible increase in Ca2+ current amplitude. Possible explanations for these findings include either cell swelling or neurite outgrowth enhancement of CSMG neurons from septic rats. Additionally, a significant rightward shift of the concentration-response relationship for the norepinephrine (NE)-mediated Ca2+ current inhibition was observed in CSMG neurons from septic rats. Testing for the presence of opioid receptor subtypes in CSMG neurons, showed that mu opioid receptors were present in ~70% of CSMG, while NOP opioid receptors were found in all CSMG neurons tested. The pharmacological profile for both opioid receptor subtypes was not significantly affected by sepsis. Further, the Ca2+ current modulation by propionate, an agonist for the free fatty acid receptors GPR41 and GPR43, was not altered by sepsis. Overall, our findings suggest that CSMG function is affected by sepsis via changes in cell size and α2-adrenergic receptor-mediated Ca2+ channel modulation.
- Subjects :
- Animals
Ganglia, Sympathetic drug effects
Ganglia, Sympathetic pathology
Ligation
Male
Mesentery metabolism
Mesentery pathology
Norepinephrine pharmacology
Organ Culture Techniques
Patch-Clamp Techniques
Propionates pharmacology
Rats, Sprague-Dawley
Receptors, G-Protein-Coupled agonists
Sepsis etiology
Calcium Channels metabolism
Ganglia, Sympathetic metabolism
Mesentery innervation
Receptors, G-Protein-Coupled metabolism
Sepsis metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 10
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 26017846
- Full Text :
- https://doi.org/10.1371/journal.pone.0125566