scholarly journals Ionic mechanisms of action potential propagation velocity changes in peripheral C-fibers. Implications for pain

2012 ◽  
Vol 13 (S1) ◽  
Author(s):  
Sten A Andersson ◽  
Marcus E Petersson ◽  
Erik Fransén
Keyword(s):  
Action Potential ◽  
Propagation Velocity ◽  
Mechanisms Of Action ◽  
Action Potential Propagation ◽  
C Fibers ◽  
Ionic Mechanisms ◽  
Velocity Changes

Ionic Mechanisms of Action of Neurotensin in Acutely Dissociated Neurons From the Diagonal Band of Broca of the Rat

1999 ◽  
Vol 81 (1) ◽  
pp. 234-246 ◽  
Author(s):  
Balvinder S. Jassar ◽  
Kim H. Harris ◽  
Paula M. Ostashewski ◽  
Jack H. Jhamandas
Keyword(s):  
Calcium Channels ◽  
Action Potential ◽  
Physiological Mechanism ◽  
Mechanisms Of Action ◽  
Calcium Currents ◽  
Whole Cell ◽  
Diagonal Band ◽  
Outward Currents ◽  
Ionic Mechanisms ◽  
Diagonal Band Of Broca

Jassar, Balvinder S., Kim H. Harris, Paula M. Ostashewski, and Jack H. Jhamandas. Ionic mechanisms of action of neurotensin in acutely dissociated neurons from the diagonal band of Broca of the rat. J. Neurophysiol. 81: 234–246, 1999. Whole cell recordings were performed on acutely dissociated neurons from the horizontal limb of the diagonal band of Broca (hDBB) from rats to elucidate the ionic mechanisms of action of neurotensin. Neurotensin caused a decrease in whole cell voltage-activated outward currents and failed to elicit a response when Ca2+ influx was blocked by changing the external solution to the one containing 0 mM Ca2+ and 50 μM Cd2+, suggesting the involvement of Ca2+-dependent conductances. Charybdotoxin, a specific blocker of voltage-sensitive calcium-activated K+ channels ( I C), caused a decrease in outward currents comparable with that caused by blocking calcium influx and occluded the neurotensin-induced decrease in outward currents. Similarly, 50 μM tetraethylammonium ions also blocked the neurotensin response. Also neurotensin reduced whole cell barium currents ( I Ba) and calcium currents ( I Ca). Amiloride and ω-conotoxin GVIA, but not nimodipine, were able to eliminate the neurotensin-induced decrease in I Ba. Thus T- and N- but not L-type calcium channels are subject to modulation by neurotensin, and this may account for its effects on I C. The predicted changes in action potential as a result of the blockade of currents through calcium channels culminating into changes in I C were confirmed in the bridge current-clamp recordings. Specifically, neurotensin application led to depolarization of the resting membrane potential, broadening of spike and a decrease in afterhyperpolarization and accommodation. These alterations in action potential characteristics that resulted in increased firing rate and excitability of the hDBB neurons also were produced by application of charybdotoxin. Neurotensin effects on these properties were occluded  by  2 - [(1 – 7 - chloro - 4 - quinolinyl) - 5 - (2, 6 - di - methoxyphenyl) pyrazol-3-yl) carbonylamino] tricyclo (3.3.1.1.)decan-2-carboxylic acid, a nonpeptide high-affinity neurotensin receptor antagonist. Neurotensin blockade of I C, possibly through I Ca, is a potential physiological mechanism whereby this peptide may evoke alterations in the cortical arousal, sleep-wake cycle, and theta rhythm.

scholarly journals Role of prostaglandin D2 in mast cell activation-induced sensitization of esophageal vagal afferents

2013 ◽  
Vol 304 (10) ◽  
pp. G908-G916 ◽  
Author(s):  
Shizhong Zhang ◽  
Gintautas Grabauskas ◽  
Xiaoyin Wu ◽  
Moon Kyung Joo ◽  
Andrea Heldsinger ◽  
...  
Keyword(s):  
Mast Cell ◽  
Action Potential ◽  
Cell Activation ◽  
Vagal Afferents ◽  
Mast Cell Activation ◽  
Lipid Mediator ◽  
Prostaglandin D2 ◽  
Patch Clamp Recording ◽  
C Fibers ◽  
Ganglion Neurons

Sensitization of esophageal afferents plays an important role in esophageal nociception, but the mechanism is less clear. Our previous studies demonstrated that mast cell (MC) activation releases the preformed mediators histamine and tryptase, which play important roles in sensitization of esophageal vagal nociceptive C fibers. PGD2 is a lipid mediator released by activated MCs. Whether PGD2 plays a role in this sensitization process has yet to be determined. Expression of the PGD2 DP1 and DP2 receptors in nodose ganglion neurons was determined by immunofluorescence staining, Western blotting, and RT-PCR. Extracellular recordings were performed in ex vivo esophageal-vagal preparations. Action potentials evoked by esophageal distension were compared before and after perfusion of PGD2, DP1 and DP2 receptor agonists, and MC activation, with or without pretreatment with antagonists. The effect of PGD2 on 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate (DiI)-labeled esophageal nodose neurons was determined by patch-clamp recording. Our results demonstrate that DP1 and DP2 receptor mRNA and protein were expressed mainly in small- and medium-diameter neurons in nodose ganglia. PGD2 significantly increased esophageal distension-evoked action potential discharges in esophageal nodose C fibers. The DP1 receptor agonist BW 245C mimicked this effect. PGD2 directly sensitized DiI-labeled esophageal nodose neurons by decreasing the action potential threshold. Pretreatment with the DP1 receptor antagonist BW A868C significantly inhibited PGD2 perfusion- or MC activation-induced increases in esophageal distension-evoked action potential discharges in esophageal nodose C fibers. In conclusion, PGD2 plays an important role in MC activation-induced sensitization of esophageal nodose C fibers. This adds a novel mechanism of visceral afferent sensitization.

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