scholarly journals Identification of Chloride Channels CLCN3 and CLCN5 Mediating the Excitatory Cl− Currents Activated by Sphingosine-1-Phosphate in Sensory Neurons

2018 ◽  
Vol 11 ◽  
Author(s):  
Yanmei Qi ◽  
Norbert Mair ◽  
Kai K. Kummer ◽  
Michael G. Leitner ◽  
María Camprubí-Robles ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Chloride Channels ◽  
Sphingosine 1 Phosphate

Cranial Nerves I and II

2021 ◽  
pp. 115-119
Author(s):  
Kelly D. Flemming ◽  
Eduardo E. Benarroch
Keyword(s):  
Optic Nerve ◽  
Sensory Neurons ◽  
Chloride Channels ◽  
Calcium Influx ◽  
Cranial Nerves ◽  
Sensory Information ◽  
Olfactory Receptors ◽  
Olfactory Nerve ◽  
Afferent Nerve ◽  
Gated Channel

Cranial nerves I (olfactory nerve) and II (optic nerve) are supratentorial, paired cranial nerves. This chapter provides an overview of their anatomy. Cranial nerve I is a special visceral afferent nerve carrying sensory information about odors. Olfactory receptors lie in the nasal cavity. Odorants activate receptors within the cilia of olfactory sensory neurons and trigger the opening of a cyclic nucleotide–gated channel. This channel allows a calcium influx and the opening of calcium-activated chloride channels. Depolarization then occurs.

Sphingosine-1-Phosphate Via Activation of a G-Protein-Coupled Receptor(s) Enhances the Excitability of Rat Sensory Neurons

2006 ◽  
Vol 96 (3) ◽  
pp. 1042-1052 ◽  
Author(s):  
Y. H. Zhang ◽  
J. C. Fehrenbacher ◽  
M. R. Vasko ◽  
G. D. Nicol
Keyword(s):  
G Protein ◽  
Sensory Neurons ◽  
Small Diameter ◽  
G Protein Coupled Receptors ◽  
External Application ◽  
Nociceptive Neurons ◽  
Firing Threshold ◽  
Current Ramp ◽  
Sphingosine 1 Phosphate ◽  
G Protein Coupled

Sphingosine-1-phosphate (S1P) is released by immune cells and is thought to play a key role in chemotaxis and the onset of the inflammatory response. The question remains whether this lipid mediator also contributes to the enhanced sensitivity of nociceptive neurons that is associated with inflammation. Therefore we examined whether S1P alters the excitability of small diameter, capsaicin-sensitive sensory neurons by measuring action potential (AP) firing and two of the membrane currents critical in regulating the properties of the AP. External application of S1P augments the number of APs evoked by a depolarizing current ramp. The enhanced firing is associated with a decrease in the rheobase and an increase in the resistance at firing threshold although neither the firing threshold nor the resting membrane potential are changed. Treatment with S1P enhanced the tetrodotoxin-resistant sodium current and decreased the total outward potassium current ( IK). When sensory neurons were internally perfused with GDP-β-S, a blocker of G protein activation, the S1P-induced increase in APs was completely blocked and suggests the excitatory actions of S1P are mediated through G-protein-coupled receptors called endothelial differentiation gene or S1PR. In contrast, internal perfusion with GDP-β-S and S1P increased the number of APs evoked by the current ramp. These results and our finding that the mRNAs for S1PRs are expressed in both the intact dorsal root ganglion and cultures of adult sensory neurons supports the notion that S1P acts on S1PRs linked to G proteins. Together these findings demonstrate that S1P can regulate the excitability of small diameter sensory neurons by acting as an external paracrine-type ligand through activation of G-protein-coupled receptors and thus may contribute to the hypersensitivity during inflammation.

scholarly journals Sphingosine 1-Phosphate to p38 Signaling via S1P1 Receptor and Gαi/o Evokes Augmentation of Capsaicin-Induced Ionic Currents in Mouse Sensory Neurons

2014 ◽  
Vol 10 ◽  
pp. 1744-8069-10-74 ◽  
Author(s):  
Michiel Langeslag ◽  
Serena Quarta ◽  
Michael G Leitner ◽  
Michaela Kress ◽  
Norbert Mair
Keyword(s):  
Sensory Neurons ◽  
Ionic Currents ◽  
S1p1 Receptor ◽  
Sphingosine 1 Phosphate

scholarly journals Sphingosine 1-phosphate receptor 2 antagonist JTE-013 increases the excitability of sensory neurons independently of the receptor

2012 ◽  
Vol 108 (5) ◽  
pp. 1473-1483 ◽  
Author(s):  
Chao Li ◽  
Xian Xuan Chi ◽  
Wenrui Xie ◽  
J. A. Strong ◽  
J.-M. Zhang ◽  
...  
Keyword(s):  
G Protein ◽  
Sensory Neurons ◽  
Neuronal Excitability ◽  
Small Diameter ◽  
G Protein Coupled Receptors ◽  
Prostaglandin E ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Sphingosine 1 Phosphate ◽  
G Protein Coupled

Previously we demonstrated that sphingosine 1-phosphate receptor 1 (S1PR1) played a prominent, but not exclusive, role in enhancing the excitability of small-diameter sensory neurons, suggesting that other S1PRs can modulate neuronal excitability. To examine the potential role of S1PR2 in regulating neuronal excitability we used the established selective antagonist of S1PR2, JTE-013. Here we report that exposure to JTE-013 alone produced a significant increase in excitability in a time- and concentration-dependent manner in 70–80% of recorded neurons. Internal perfusion of sensory neurons with guanosine 5′- O-(2-thiodiphosphate) (GDP-β-S) via the recording pipette inhibited the sensitization produced by JTE-013 as well as prostaglandin E2. Pretreatment with pertussis toxin or the selective S1PR1 antagonist W146 blocked the sensitization produced by JTE-013. These results indicate that JTE-013 might act as an agonist at other G protein-coupled receptors. In neurons that were sensitized by JTE-013, single-cell RT-PCR studies demonstrated that these neurons did not express the mRNA for S1PR2. In behavioral studies, injection of JTE-013 into the rat's hindpaw produced a significant increase in the mechanical sensitivity in the ipsilateral, but not contralateral, paw. Injection of JTE-013 did not affect the withdrawal latency to thermal stimulation. Thus JTE-013 augments neuronal excitability independently of S1PR2 by unknown mechanisms that may involve activation of other G protein-coupled receptors such as S1PR1. Clearly, further studies are warranted to establish the causal nature of this increased sensitivity, and future studies of neuronal function using JTE-013 should be interpreted with caution.

scholarly journals Calcium-activated chloride channels in the apical region of mouse vomeronasal sensory neurons

2012 ◽  
Vol 140 (1) ◽  
pp. 3-15 ◽  
Author(s):  
Michele Dibattista ◽  
Asma Amjad ◽  
Devendra Kumar Maurya ◽  
Claudia Sagheddu ◽  
Giorgia Montani ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Chloride Channels ◽  
Calcium Concentration ◽  
Transient Receptor Potential ◽  
Flash Photolysis ◽  
Physiological Role ◽  
Disulfonic Acid ◽  
Apical Region ◽  
Caged Calcium ◽  
Vomeronasal Sensory Neurons

The rodent vomeronasal organ plays a crucial role in several social behaviors. Detection of pheromones or other emitted signaling molecules occurs in the dendritic microvilli of vomeronasal sensory neurons, where the binding of molecules to vomeronasal receptors leads to the influx of sodium and calcium ions mainly through the transient receptor potential canonical 2 (TRPC2) channel. To investigate the physiological role played by the increase in intracellular calcium concentration in the apical region of these neurons, we produced localized, rapid, and reproducible increases in calcium concentration with flash photolysis of caged calcium and measured calcium-activated currents with the whole cell voltage-clamp technique. On average, a large inward calcium-activated current of −261 pA was measured at −50 mV, rising with a time constant of 13 ms. Ion substitution experiments showed that this current is anion selective. Moreover, the chloride channel blockers niflumic acid and 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid partially inhibited the calcium-activated current. These results directly demonstrate that a large chloride current can be activated by calcium in the apical region of mouse vomeronasal sensory neurons. Furthermore, we showed by immunohistochemistry that the calcium-activated chloride channels TMEM16A/anoctamin1 and TMEM16B/anoctamin2 are present in the apical layer of the vomeronasal epithelium, where they largely colocalize with the TRPC2 transduction channel. Immunocytochemistry on isolated vomeronasal sensory neurons showed that TMEM16A and TMEM16B coexpress in the neuronal microvilli. Therefore, we conclude that microvilli of mouse vomeronasal sensory neurons have a high density of calcium-activated chloride channels that may play an important role in vomeronasal transduction.

scholarly journals Expression of sphingosine 1-phosphate receptors in the rat dorsal root ganglia and defined single isolated sensory neurons

2012 ◽  
Vol 44 (18) ◽  
pp. 889-901 ◽  
Author(s):  
J. S. Kays ◽  
Chao Li ◽  
G. D. Nicol
Keyword(s):  
Sensory Neurons ◽  
Dorsal Root ◽  
Neuronal Excitability ◽  
Expression Profiles ◽  
Large Diameter ◽  
Small Diameter ◽  
Positive Control ◽  
Single Neurons ◽  
Sphingosine 1 Phosphate ◽  
S1p Receptor

Previously, we demonstrated that sphingosine 1-phosphate (S1P) increased the excitability of small-diameter sensory neurons, in part, through activation of S1P receptor 1 (S1PR1), suggesting that other S1PRs can modulate neuronal excitability. Therefore, studies were undertaken to establish the expression profiles of S1PRs in the intact dorsal root ganglion (DRG) and in defined single isolated sensory neurons. To determine mRNA expression of S1PRs in the DRG, SYBR green quantitative PCR (qPCR) was used. To determine the expression of S1PR mRNAs in single neurons of defined diameters, a preamplification protocol utilizing Taqman primer and probes was used to enhance the sensitivity of detection. The preamplification protocol also permitted detection of mRNA for two hallmark neuronal receptor/ion channels, TRPV1 and P2X3. Expression profiles of S1PR mRNA isolated from lung and brain were used as positive control tissues. In the intact DRG, the order of expression of S1PRs was S1PR3>>R1≈R2>R5≈R4. In the single neurons, the expression of S1PRs was quite variable with some neurons expressing all five subtypes, whereas some expressing only one subtype. In contrast to the DRG, S1PR1 was the highest expressing subtype in 10 of the 18 small-, medium-, and large-diameter sensory neurons. S1PR1 was the second highest expressor in ∼50% of those remaining neurons. Overall, in the single neurons, the order of expression was S1PR1>>R3≈R5>R4>R2. The results obtained from the single defined neurons are consistent with our previous findings wherein S1PR1 plays a prominent but not exclusive role in the enhancement of neuronal excitability.

scholarly journals The Sphingosine 1-Phosphate Receptor, S1PR1, Plays a Prominent But Not Exclusive Role in Enhancing the Excitability of Sensory Neurons

2010 ◽  
Vol 104 (5) ◽  
pp. 2741-2748 ◽  
Author(s):  
Xian Xuan Chi ◽  
G. D. Nicol
Keyword(s):  
Sensory Neurons ◽  
Small Diameter ◽  
Cell Types ◽  
G Protein Coupled Receptors ◽  
Rt Pcr ◽  
Additional Increase ◽  
Sphingosine 1 Phosphate ◽  
Subsequent Exposure ◽  
G Protein Coupled

Sphingosine 1-phosphate (S1P) through its interaction with a family of G protein–coupled receptors (S1PR) is proving to have a significant impact on the activation of a variety of cell types, most notably those cells mediating the inflammatory response. Previously, we showed that S1P enhanced the excitability of small diameter sensory neurons, and mRNA for S1PR1–4 was expressed in sensory neurons. These initial findings did not determine which S1PR subtype(s) mediated the increased excitability. Here, we report that exposure to the selective S1PR1 agonist, SEW2871, produced a significant increase in excitability of some, but not all, sensory neurons. To further examine the role of S1PR1, neurons were treated with siRNA targeted to S1PR1. siRNA reduced S1PR1 protein expression by 75% and blocked the sensitization produced by SEW2871, although some neurons remained responsive to subsequent exposure to S1P. Treatment with scramble siRNA did not alter S1PR1 expression. Recordings from siRNA- and scramble-treated neurons suggested three distinct populations based on their sensitivities to SEW2871 and S1P. Approximately 50% of the neurons exhibited a significant increase in excitability after exposure to SEW2871 and subsequent S1P produced no additional increase; ∼25% were not affected by SEW2871 but S1P significantly increased excitability; and ∼25% of the neurons were not sensitized by either SEW2871 or S1P. RT-PCR measurements obtained from single neurons showed that 50% of the small diameter neurons expressed the mRNA for S1PR1. These results indicate that S1PR1 plays a prominent, although not exclusive, role in mediating the enhancement of excitability produced by S1P.

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