Excitability of small-diameter trigeminal ganglion neurons by 5-HT is mediated by enhancement of the tetrodotoxin-resistant sodium current due to the activation of 5-HT4 receptors and/or by the inhibition of the transient potassium current

Tsutsui, Yukako; Ikeda, Mizuho; Takeda, Masatoshi; Matsumoto, Shigeji

doi:10.1016/j.neuroscience.2008.09.024

Cited by 9 publications

(5 citation statements)

References 44 publications

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“…Notably, both AKAP6 and 5‐HT are associated with the cyclic adenosine monophosphate (cAMP) signaling pathway. Because 5‐HT exerts its effect through the cAMP effector pathway,36 which is coordinated by AKAP6,37 the crosstalk between AKAP6 and HTR1E on bone metabolism warrants further investigation. The third gene, whose SNPs were highly suggestively associated with PC4 in women only, was the COL4A2 gene.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association of an integrated osteoporosis-related phenotype: Is there evidence for pleiotropic genes?

Karasik

Cheung

Zhou

et al. 2011

Journal of Bone and Mineral Research

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Multiple musculoskeletal traits assessed by various methods at different skeletal sites serve as surrogates for osteoporosis risk. However, it is a challenge to select the most relevant phenotypes for genetic study of fractures. Principal component analyses (PCA) were conducted in participants of the Framingham Osteoporosis Study on 17 measures including BMD (hip and spine), heel ultrasound, leg lean mass (LLM), and hip geometric indices, adjusting for covariates (age, height, BMI), in a combined sample of 1,180 men and 1,758 women, as well as in each sex. Four principal components (PCs) jointly explained ~69% of the total variability of musculoskeletal traits. PC1, explaining ~33% of the total variance, was referred to as the component of “Bone strength”, since it included the hip and spine BMD as well as several hip cross-sectional properties. PC2 (20.5% variance) was labeled as “Femoral cross-sectional geometry“; PC3 (~8% variance) captured only ultrasound measures; PC4, explaining ~7% variance, was correlated with LLM and hip geometry. We then evaluated ~2,5 mil SNPs for association with PCs 1, 2, and 4. There were genome-wide significant associations (p < 5 × 10−8) between PC2 and HTR1E (that codes for one of the serotonin receptors) and PC4 with COL4A2 in women. In the sexes-combined sample, AKAP6 was associated with PC2 (p= 1.40 × 10−7). A SNP in HTR1E was also associated with the risk of non-vertebral fractures in women (p= 0.005). Functions of top associated genes were enriched for the skeletal and muscular system development (p < 0.05). In conclusion, multivariate combination provides genetic associations not identified in the analysis of primary phenotypes. Genome-wide screening for the linear combinations of multiple osteoporosis-related phenotypes suggests that there are variants with potentially pleiotropic effects in established and novel pathways to be followed up to provide further evidence of their functions.

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Section: Discussionmentioning

confidence: 99%

Genome-wide association of an integrated osteoporosis-related phenotype: Is there evidence for pleiotropic genes?

Karasik

Cheung

Zhou

et al. 2011

Journal of Bone and Mineral Research

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“…Current injections for 300 ms were applied in increments of 50 pA. Action potentials were initially evoked by a depolarizing pulse at one threshold (1 T); the action potential number was measured during 3 times T (3 T). We classified NG neurons as slowly adapting (SA)‐type NG neurons, as described in previous studies [22–24]. During current injection at 3T, we determined whether AZ has 4‐AP‐like effects on the action potential in NG neurons showing multiple action potentials of more than two spikes.…”

Section: Methodsmentioning

confidence: 99%

Effects of Acetazolamide on Transient K+ Currents and Action Potentials in Nodose Ganglion Neurons of Adult Rats

Matsumoto

Yoshida

Ikeda

et al. 2011

CNS Neuroscience &Amp; Therapeutics

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The aim of the present study was to determine whether acetazolamide (AZ) contributes to the inhibition of the fast inactivating transient K+ current (IA) in adult rat nodose ganglion (NG) neurons. We have previously shown that pretreatment with either AZ or 4-AP attenuated or blocked the CO2-induced inhibition of slowly adapting pulmonary stretch receptors in in vivo experiments. The patch-clamp experiments were performed by using the isolated NG neurons. In addition to this, the RT-PCR of mRNA and the expression of voltage-gated K+ (Kv) 1.4, Kv 4.1, Kv 4.2, and Kv 4.3 channel proteins from nodose ganglia were examined. We used NG neurons sensitive to the 1 mM AZ application. The application of 1 mM AZ inhibited the IA by approximately 27% and the additional application of 4-AP (1 mM) further inhibited IA by 48%. The application of 0.1 μM α-dendrotoxin (α-DTX), a slow inactivating transient K+ current (ID) blocker, inhibited the baseline IA by approximately 27%, and the additional application of 1 mM AZ further decreased the IA by 51%. In current clamp experiments, AZ application (1 mM) increased the number of action potentials due to the decreased duration of the depolarizing phase of action potentials and/or due to a reduction in the resting membrane potential. Four voltage-gated K+ channel proteins were present, and most (80–90%) of the four Kv channels immunoreactive neurons showed the co-expression of carbonic anhydrase-II (CA-II) immunoreactivity. These results indicate that the application of AZ causes the reduction in IA via the inhibition of four voltage-gated K+ channel (Kv) proteins without affecting ID.

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“…When AP and AHP features were compared between TRG and DRG cell types, the difference of current injection protocols between the present TRG and earlier DRG studies should be noted. The long current injection used in the present study has frequently been used to generate AP and AHP in many other TRG in vitro studies (López de Armentia et al 2000;Park et al 2009;Takeda et al 2004aTakeda et al ,b, 2005Takeda et al , 2006Tsutsui et al 2008;Veiga Moreira et al 2007;Yoshida and Matsumoto 2005;Yoshida et al 2007). The durations of AP and AHP are thought to be prolonged and shortened, respectively, by the injected current compared with those of physiologically induced AP and AHP in vivo.…”

Section: Ap Features In Trg Cellsmentioning

confidence: 97%

“…Many studies have reported current signatures of I H , I A , and voltage-activated Na ϩ inward currents in TRG neurons (Ikeda and Matsumoto 2003;Matsumoto et al 2010;Takeda et al 2002Takeda et al , 2004aTakeda et al ,b, 2006Tsutsui et al 2008;Yoshida and Matsumoto 2005;Yoshida et al 2007). Because the TRG is generally thought to have a neuronal population comparable to that of the DRG, the current signature classification may be available to separate TRG cells into many internally homogeneous cell types that are distinct from other subclassified cell types.…”

Section: Introductionmentioning

confidence: 99%

Electrophysiological and Chemical Properties in Subclassified Acutely Dissociated Cells of Rat Trigeminal Ganglion by Current Signatures

Ono

Inenaga

2010

Journal of Neurophysiology

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Xu S, Ono K, Inenaga K. Electrophysiological and chemical properties in subclassified acutely dissociated cells of rat trigeminal ganglion by current signatures. J Neurophysiol 104: 3451-3461, 2010. First published June 23, 2010 doi:10.1152/jn.00336.2010. In the present study, we subclassified acutely dissociated trigeminal ganglion (TRG) cells of rats using a current signature method in whole cell patch-clamp recordings. Using modified criteria for cell classification for the dorsal root ganglion (DRG), TRG cells were subclassified into nine cell types: 1-5, 7-9, and 13. Types 1, 3, and 7 were in the small cell groups (15-24 m); types 4, 5, and 8 -13 were in the medium cell groups (25-38 m); and type 2 was a mixed group of both cell sizes. Types 1-3, 5, and 7 showed high-input resistance and types 1, 2, and 7 showed more depolarized resting membrane potentials. Types 1, 2, and 5-13 expressed long-duration action potentials (APs), but types 3 and 4 expressed short-duration APs. Sensitivities to capsaicin, protons, and adenosine 5=-triphosphate (ATP) in TRG cell types largely corresponded to DRG cell types. However, different from the matched DRG types, half of TRG type 1 cells were capsaicin insensitive, showing desensitizing proton-induced currents, and types 5, 7, and 9 exhibited slow-desensitizing ATP-induced currents. Types 4, 5, and 8 -13 had nicotine sensitivity, but the other cell types were insensitive. These results indicate that the "current signatures" classification is a useful means to separate TRG cells into internally homogeneous subpopulations that were distinct from other cell types. Furthermore, the data suggest some specific differences in the chemical responsiveness of some cell types between the TRG and DRG.

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Excitability of small-diameter trigeminal ganglion neurons by 5-HT is mediated by enhancement of the tetrodotoxin-resistant sodium current due to the activation of 5-HT4 receptors and/or by the inhibition of the transient potassium current

Cited by 9 publications

References 44 publications

Genome-wide association of an integrated osteoporosis-related phenotype: Is there evidence for pleiotropic genes?

Genome-wide association of an integrated osteoporosis-related phenotype: Is there evidence for pleiotropic genes?

Effects of Acetazolamide on Transient K+ Currents and Action Potentials in Nodose Ganglion Neurons of Adult Rats

Electrophysiological and Chemical Properties in Subclassified Acutely Dissociated Cells of Rat Trigeminal Ganglion by Current Signatures

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