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Cinda J. Helke - One of the best experts on this subject based on the ideXlab platform.
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Axotomy alters neurotrophin and neurotrophin receptor mRNAs in the vagus nerve and Nodose Ganglion of the rat
Molecular Brain Research, 2001Co-Authors: Huang Zhuo, Cinda J. HelkeAbstract:Abstract Neurotrophins and neurotrophin receptors play an important role in survival and growth of injured peripheral nerves. To study the injury-mediated neurotrophic response in autonomic nerves, we investigated changes in mRNA expression of neurotrophins and their receptors in the transected vagus nerve and Nodose Ganglion. Studies using in situ hybridization histochemistry showed that axotomy of the cervical vagus nerve resulted in increased expression of mRNAs for nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3), and for TrkA, TrkB, and TrkC receptors in non-neuronal cells at both the proximal and distal segments of the transected cervical vagus nerve. Moreover, NGF protein was increased in the distal end, and NT-3 protein was increased in both the proximal and the distal ends of the transected nerve 3 days after axotomy. No change of p75NTR mRNA was detected in the transected vagus nerve. The induction of each neurotrophin and Trk receptor mRNA was apparent within 1 day after the axotomy and was sustained at least 14 days. By 45 days after the axotomy, a time when axonal reconnection with target tissue is made (integrity of the nerve-target connection was confirmed by the retrograde transport of FluoroGold from the stomach to vagal cell bodies), the levels of neurotrophin and Trk mRNAs in the vagus nerve declined to pre-axotomy levels. TrkA, TrkC, and p75NTR mRNA-containing vagal sensory neurons in the Nodose Ganglion were reduced in number after cervical vagotomy. Neurotrophin-mRNA-containing neurons were not found in the Nodose ganglia from either intact or vagotomized rats. The axotomy-induced up-regulation of neurotrophins and Trk receptors mainly in the non-neuronal cells at or near the site of transection suggests that neurotrophins are involved in the survival and regeneration process of the vagus nerve after injury.
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Neurochemistry of the Nodose Ganglion.
Progress in Neurobiology, 1997Co-Authors: H. Zhuo, H. Ichikawa, Cinda J. HelkeAbstract:Abstract Placode-derived general visceral afferent neurons of the Nodose Ganglion transmit visceral sensory information from specialized sensory endings of the vagus nerve and its branches to the nucleus of the solitary tract. These neurons are critical in relaying information such as elevations in blood pressure, changes in blood oxygenation, passage of contents through the esophagus and intestines, and distention of the heart, stomach, and lungs to the CNS for reflex maintenance of visceral functions. Multiple neurotransmitters, neuropeptides, calcium binding proteins, and other neuroactive substances are associated with neurons of the Nodose Ganglion. Many neurons colocalize 2 or more neuroactive substances creating the potential for complex interactions of neurochemical signals in the NTS. Neurons of the Nodose Ganglion also contain a variety of receptors which respond to transmitters, inflammatory mediators, and neurotrophic factors. The contents of these neurochemicals and receptors are not static as alterations in their expression are noted in response to epigenetic influences. Although not yet well understood, potential factors and mechanisms regulating neurochemical events in the Nodose Ganglion neurons are discussed. Published by Elsevier Science Ltd.
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Neurochemistry of the Nodose Ganglion.
Progress in neurobiology, 1997Co-Authors: H. Zhuo, H. Ichikawa, Cinda J. HelkeAbstract:Placode-derived general visceral afferent neurons of the Nodose Ganglion transmit visceral sensory information from specialized sensory endings of the vagus nerve and its branches to the nucleus of the solitary tract. These neurons are critical in relaying information such as elevations in blood pressure, changes in blood oxygenation, passage of contents through the esophagus and intestines, and distention of the heart, stomach, and lungs to the CNS for reflex maintenance of visceral functions. Multiple neurotransmitters, neuropeptides, calcium binding proteins, and other neuroactive substances are associated with neurons of the Nodose Ganglion. Many neurons colocalize 2 or more neuroactive substances creating the potential for complex interactions of neurochemical signals in the NTS. Neurons of the Nodose Ganglion also contain a variety of receptors which respond to transmitters, inflammatory mediators, and neurotrophic factors. The contents of these neurochemicals and receptors are not static as alterations in their expression are noted in response to epigenetic influences. Although not yet well understood, potential factors and mechanisms regulating neurochemical events in the Nodose Ganglion neurons are discussed.
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inhibition of axoplasmic transport in the rat vagus nerve alters the numbers of neuropeptide and tyrosine hydroxylase messenger rna containing and immunoreactive visceral afferent neurons of the Nodose Ganglion
Neuroscience, 1995Co-Authors: Huang Zhuo, A C Lewin, E T Phillips, C Sinclair, Cinda J. HelkeAbstract:Abstract Previous work showed that axotomy-induced deafferentation of the placode-derived visceral afferent neurons of the Nodose Ganglion altered their expression of some neuropeptides and tyrosine hydroxylase. The present studies were designed to selectively evaluate the loss of axonal transport on the numbers of vasoactive intestinal polypeptide, tyrosine hydroxylase, and calcitonin gene-related peptide mRNA-containing and immunoreactive neurons in the Nodose Ganglion of the adult rat. Vinblastine (0.15 mM) application to the cervical vagus nerve was used to block axonal tranport between Ganglionic perikarya and peripheral targets. In situ hybridization histochemistry with 35 S-labeled oligonucleotide probes was used to both quantify the number of mRNA-containing neurons and to assess the density of mRNA expression per neuron, and immunocytochemistryk was used to visualize the number of immunoreactive neurons. The efficacy of vinblastine to inhibit axonal transport was verified by evaluating the build-up of calcitonin gene-related peptide immunoreactive in the vagus nerve immediately rostral to the site of drug application. The absence of vinblastine-induced neuronal damage was verified by the relative absence of degenerating nerves in the vagus nerve caudal to the site of drug application. Vinblastine treatment of the vagus nerve increased the numbers of vasoactive intestinal peptide mRNA-containing neurons and vasoactive intestinal peptide-immunoreactive neurons in the Nodose Ganglion at three, seven and 14 days, and increased the numbers of calcitonin gene-related peptide mRNA-containing and calcitonin gene-related peptide-immunoreactive neurons in the Nodose Ganglion at one, three and seven days. The average labeling density of vasoactive intestinal peptide mRNA-containing neurons was also increased following vinblastine treatment. Vinblastine treatment of the cervical vagus nerve, however, led to the appearance of low-labeling density calcitonin gene-related peptide mRNA-neurons and resulted in reduction of the average labeling density for calcitonin gene-related peptide mRNA-containing neurons. In contrast, application of vinblastine to the cervical vagus nerve, decreased the number of tyrosine hydroxylase mRNA-containing and tyrosine hydroxylase-immunoreactive neurons in the Nodose Ganglion. In summary, inhibition of the axoplasmic transport between the periphery and the visceral sensory perikarya appeared to alter vasoactive intestinal peptide, calcitonin gene-related peptide, and tyrosine hydroxylase expression and content in visceral sensory neurons of the Nodose Ganglion. These data suggest the presence of an axonally transported influence on the regulation of neuropeptide and neurotransmitter enzyme synthesis in mature placode-derived visceral sensory neurons.
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Plasticity of tyrosine hydroxylase and vasoactive intestinal peptide messenger RNAs in visceral afferent neurons of the Nodose Ganglion upon axotomy-induced deafferentation
Neuroscience, 1994Co-Authors: Huang Zhuo, C.m. Sinclair, Cinda J. HelkeAbstract:Abstract The Nodose Ganglion contains placode-derived visceral sensory neurons of the vagus nerve. Previous study showed that axotomy-induced deafferentation reduced the number of tyrosine hydroxylaseimmunoreactive and increased the number of vasoactive intestinal peptide-immunoreactive neurons in the Ganglion. The present study was conducted to determine whether the changes in neuropeptide/neurotransmitter enzyme content are associated with changes in the expression of tyrosine hydroxylase and vasoactive intestinal peptide messenger RNAs in the Nodose Ganglion. We used in situ hybridization histochemistry with 35 S-labeled oligonucleotide probes for tyrosine hydroxylase and vasoactive intestinal peptide precursor messenger RNAs. Peripheral axotomy of visceral afferent inputs reduced tyrosine hydroxylase messenger RNA and increased vasoactive intestinal peptide messenger RNA expression in neurons of the Nodose Ganglion of the rat. The number of tyrosine hydroxylase messenger RNA-containing neurons was significantly reduced at three, seven and 14 days after axotomy-induced deafferentation compared with intact and sham-operated controls. Labeling density of tyrosine hydroxylase messenger RNA-containing neurons was significantly reduced at three and seven days. Conversely, the number of vasoactive intestinal peptide messenger RNA-containing neurons increased significantly at three, seven and 14 days, while the labeling density of vasoactive intestinal peptide messenger RNA-containing neurons also increased at one, three, seven and 14 days. The results of the present study indicate that the axotomy-induced down-regulation of tyrosine hydroxylase and up-regulation of vasoactive intestinal peptide in the neurons of the Nodose Ganglion are associated with changes in their messenger RNAs in response to axotomy-induced deafferentation.
Baofeng Yang - One of the best experts on this subject based on the ideXlab platform.
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inhibitory effects of artemisinin on voltage gated ion channels in intact Nodose Ganglion neurones of adult rats
Basic & Clinical Pharmacology & Toxicology, 2007Co-Authors: Guo-fen Qiao, Baofeng YangAbstract:Recent data show that artemisinin has anti-arrhythmic and local anaesthetic effects. To better understand the mechanisms, the effects of artemisinin on action potential discharge and voltage-gated ion channels properties were studied on Nodose Ganglion neurones of adult rats with known sensory afferent fibre type using whole cell patch and vagus Nodose slice preparation. The present data show that both depolarization and repolarization of action potentials were markedly inhibited by artemisinin in a concentration- and time-dependent manner in either A-type or C-type Nodose Ganglion neurones without change in conduction velocity. Both tetrodotoxin-sensitive (TTX-S) Na+ and tetrodotoxin-resistant (TTX-R) Na+ currents were significantly reduced by micro-perfusion of artemisinin; the steady-state half-activation and half-inactivation for both TTX-S and TTX-R Na+ currents were shifted towards the right without changing slope factors. Median inhibition concentration (IC50) are 68.1 microM and 236.2 microM for TTX-S and TTX-R Na+ currents, respectively. Total outward K+ currents from C-type Nodose Ganglion neurones were blocked by artemisinin 30-300 microM concentration-dependently, IC50 being 104.7 microM. This effect was mimicked by tetraethylammonium 15 mM. Peak currents of N-type Ca2+ channels were also reduced significantly (IC50=344.6 microM) in the presence of artemisinin, which was less effective than that induced by 1 microM omega-conotoxin (CTX) GIVA. Our data demonstrate that depolarization and repolarization of action potentials recorded from either A- or C-type Nodose Ganglion neurones were inhibited by artemisinin in a concentration- and time-dependent manner, and that this inhibitory effect of artemisinin is probably due to the non-selective inhibition of all major ion channels functionally expressed in Nodose Ganglion neurones.
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Inhibitory Effects of Artemisinin on Voltage‐Gated Ion Channels in Intact Nodose Ganglion Neurones of Adult Rats
Basic & clinical pharmacology & toxicology, 2007Co-Authors: Guo-fen Qiao, Baofeng YangAbstract:Recent data show that artemisinin has anti-arrhythmic and local anaesthetic effects. To better understand the mechanisms, the effects of artemisinin on action potential discharge and voltage-gated ion channels properties were studied on Nodose Ganglion neurones of adult rats with known sensory afferent fibre type using whole cell patch and vagus Nodose slice preparation. The present data show that both depolarization and repolarization of action potentials were markedly inhibited by artemisinin in a concentration- and time-dependent manner in either A-type or C-type Nodose Ganglion neurones without change in conduction velocity. Both tetrodotoxin-sensitive (TTX-S) Na+ and tetrodotoxin-resistant (TTX-R) Na+ currents were significantly reduced by micro-perfusion of artemisinin; the steady-state half-activation and half-inactivation for both TTX-S and TTX-R Na+ currents were shifted towards the right without changing slope factors. Median inhibition concentration (IC50) are 68.1 microM and 236.2 microM for TTX-S and TTX-R Na+ currents, respectively. Total outward K+ currents from C-type Nodose Ganglion neurones were blocked by artemisinin 30-300 microM concentration-dependently, IC50 being 104.7 microM. This effect was mimicked by tetraethylammonium 15 mM. Peak currents of N-type Ca2+ channels were also reduced significantly (IC50=344.6 microM) in the presence of artemisinin, which was less effective than that induced by 1 microM omega-conotoxin (CTX) GIVA. Our data demonstrate that depolarization and repolarization of action potentials recorded from either A- or C-type Nodose Ganglion neurones were inhibited by artemisinin in a concentration- and time-dependent manner, and that this inhibitory effect of artemisinin is probably due to the non-selective inhibition of all major ion channels functionally expressed in Nodose Ganglion neurones.
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Effects of artemisinin on action potentials from C-type Nodose Ganglion neurons
Acta pharmacologica Sinica, 2003Co-Authors: Guo-fen Qiao, Baofeng YangAbstract:AIM: To investigate the effects of artemisinin (Art) on the action potentials (AP) recorded from identified C-type Nodose neurons and study its anti-arrhythmic and anesthetic mechanisms. METHODS: Neonatal and adult rats were selected for the preparation of isolated Nodose ganglia neurons (NGN) and Nodose Ganglion-vagus slice preparation. Somatic AP were recorded from both isolated and slice NGN using whole-cell patch technique. Conduction velocity (CV) was measured using slice preparation. The effects of Art on AP were evaluated with the reference to ketamine. RESULTS: Effects of Art on AP were that: (1) AP depolarizing profiles were inhibited without changing resting membrane potential (RMP). The peak of AP (AP(peak)) and upstroke velocity (UV(APD50) and UV(max)) decreased markedly (P CONCLUSION: Art inhibited both depolarization and repolarization of AP, suggesting that the effects of Art were probably, due to the blockade of Na+ and K+ ion channels.
Guo-fen Qiao - One of the best experts on this subject based on the ideXlab platform.
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Subtype Identification in Acutely Dissociated Rat Nodose Ganglion Neurons Based on Morphologic
2013Co-Authors: Zhen-yu Yan, Zhao Qian, Yang Liu, Li-min Han, Guo-fen QiaoAbstract:Nodose ganglia are composed of A-, Ah- and C-type neurons. Despite their important roles in regulating visceral afferent function, including cardiovascular, pulmonary, and gastrointestinal homeostasis, information about subtype-specific expression, molecular identity, and function of individual ion transporting proteins is scarce. Although experiments utilizing the sliced Ganglion preparation have provided valuable insights into the electrophysiological properties of Nodose Ganglion neuron subtypes, detailed characterization of their electrical phenotypes will require measurements in isolated cells. One major unresolved problem, however, is the difficulty to unambiguously identify the subtype of isolated Nodose Ganglion neurons without current-clamp recording, because the magnitude of conduction velocity in the corresponding afferent fiber, a reliable marker to discriminate subtypes in situ, can no longer be determined. Here, we present data supporting the notion that application of an algorithm regarding to microscopic structural characteristics, such as neuron shape evaluated by the ratio between shortest and longest axis, neuron surface characteristics, like membrane roughness, and axon attachment, enables specific and sensitive subtype identification of acutely dissociated rat Nodose Ganglion neurons, by which the accuracy of identification is further validated by electrophysiological markers and overall positive predictive rates is 89.26% (90.04%, 76.47%, and 98.21% for A-, Ah, and C-type, respectively). This approach should aid in gaining insight into the molecular correlates underlying phenotypic heterogeneity of Nodose ganglia. Additionally, several critical points that help for neuron identification and afferent conduction calibration are also discussed.
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inhibitory effects of artemisinin on voltage gated ion channels in intact Nodose Ganglion neurones of adult rats
Basic & Clinical Pharmacology & Toxicology, 2007Co-Authors: Guo-fen Qiao, Baofeng YangAbstract:Recent data show that artemisinin has anti-arrhythmic and local anaesthetic effects. To better understand the mechanisms, the effects of artemisinin on action potential discharge and voltage-gated ion channels properties were studied on Nodose Ganglion neurones of adult rats with known sensory afferent fibre type using whole cell patch and vagus Nodose slice preparation. The present data show that both depolarization and repolarization of action potentials were markedly inhibited by artemisinin in a concentration- and time-dependent manner in either A-type or C-type Nodose Ganglion neurones without change in conduction velocity. Both tetrodotoxin-sensitive (TTX-S) Na+ and tetrodotoxin-resistant (TTX-R) Na+ currents were significantly reduced by micro-perfusion of artemisinin; the steady-state half-activation and half-inactivation for both TTX-S and TTX-R Na+ currents were shifted towards the right without changing slope factors. Median inhibition concentration (IC50) are 68.1 microM and 236.2 microM for TTX-S and TTX-R Na+ currents, respectively. Total outward K+ currents from C-type Nodose Ganglion neurones were blocked by artemisinin 30-300 microM concentration-dependently, IC50 being 104.7 microM. This effect was mimicked by tetraethylammonium 15 mM. Peak currents of N-type Ca2+ channels were also reduced significantly (IC50=344.6 microM) in the presence of artemisinin, which was less effective than that induced by 1 microM omega-conotoxin (CTX) GIVA. Our data demonstrate that depolarization and repolarization of action potentials recorded from either A- or C-type Nodose Ganglion neurones were inhibited by artemisinin in a concentration- and time-dependent manner, and that this inhibitory effect of artemisinin is probably due to the non-selective inhibition of all major ion channels functionally expressed in Nodose Ganglion neurones.
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Inhibitory Effects of Artemisinin on Voltage‐Gated Ion Channels in Intact Nodose Ganglion Neurones of Adult Rats
Basic & clinical pharmacology & toxicology, 2007Co-Authors: Guo-fen Qiao, Baofeng YangAbstract:Recent data show that artemisinin has anti-arrhythmic and local anaesthetic effects. To better understand the mechanisms, the effects of artemisinin on action potential discharge and voltage-gated ion channels properties were studied on Nodose Ganglion neurones of adult rats with known sensory afferent fibre type using whole cell patch and vagus Nodose slice preparation. The present data show that both depolarization and repolarization of action potentials were markedly inhibited by artemisinin in a concentration- and time-dependent manner in either A-type or C-type Nodose Ganglion neurones without change in conduction velocity. Both tetrodotoxin-sensitive (TTX-S) Na+ and tetrodotoxin-resistant (TTX-R) Na+ currents were significantly reduced by micro-perfusion of artemisinin; the steady-state half-activation and half-inactivation for both TTX-S and TTX-R Na+ currents were shifted towards the right without changing slope factors. Median inhibition concentration (IC50) are 68.1 microM and 236.2 microM for TTX-S and TTX-R Na+ currents, respectively. Total outward K+ currents from C-type Nodose Ganglion neurones were blocked by artemisinin 30-300 microM concentration-dependently, IC50 being 104.7 microM. This effect was mimicked by tetraethylammonium 15 mM. Peak currents of N-type Ca2+ channels were also reduced significantly (IC50=344.6 microM) in the presence of artemisinin, which was less effective than that induced by 1 microM omega-conotoxin (CTX) GIVA. Our data demonstrate that depolarization and repolarization of action potentials recorded from either A- or C-type Nodose Ganglion neurones were inhibited by artemisinin in a concentration- and time-dependent manner, and that this inhibitory effect of artemisinin is probably due to the non-selective inhibition of all major ion channels functionally expressed in Nodose Ganglion neurones.
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Effects of artemisinin on action potentials from C-type Nodose Ganglion neurons
Acta pharmacologica Sinica, 2003Co-Authors: Guo-fen Qiao, Baofeng YangAbstract:AIM: To investigate the effects of artemisinin (Art) on the action potentials (AP) recorded from identified C-type Nodose neurons and study its anti-arrhythmic and anesthetic mechanisms. METHODS: Neonatal and adult rats were selected for the preparation of isolated Nodose ganglia neurons (NGN) and Nodose Ganglion-vagus slice preparation. Somatic AP were recorded from both isolated and slice NGN using whole-cell patch technique. Conduction velocity (CV) was measured using slice preparation. The effects of Art on AP were evaluated with the reference to ketamine. RESULTS: Effects of Art on AP were that: (1) AP depolarizing profiles were inhibited without changing resting membrane potential (RMP). The peak of AP (AP(peak)) and upstroke velocity (UV(APD50) and UV(max)) decreased markedly (P CONCLUSION: Art inhibited both depolarization and repolarization of AP, suggesting that the effects of Art were probably, due to the blockade of Na+ and K+ ion channels.
Rudolf E Lang - One of the best experts on this subject based on the ideXlab platform.
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leptin receptor expression in Nodose Ganglion cells projecting to the rat gastric fundus
Neuroscience Letters, 2002Co-Authors: Christian Peiser, Jochen Springer, David A Groneberg, G P Mcgregor, Axel Fischer, Rudolf E LangAbstract:Recent studies suggest that in addition to adipocytes the chief cells of the gastric fundic mucosa are a site of leptin production. In order to assess the possible role of vagal afferent neurons in transmitting leptin signals from the stomach to the brain, leptin receptor (OB-R) expression was investigated in rat Nodose Ganglion cells and their projection to the stomach determined by retrograde tracing. Reverse transcription-polymerase chain reaction combined with laser-assisted cell picking revealed that large and small diameter neurons express both the long (OB-Rb) and short (OB-Ra) splice variants of the OB-R. OB-R like immunoreactivity was detected in the perikarya of approximately 8% of Nodose Ganglion neurons. Tracing studies revealed that a significant proportion (15%) of the immunopositive neurons projected to the gastric fundus. These findings suggest that leptin may use a neural route to relay its message from peripheral sites of leptin synthesis such as the gastric fundus to the brain.
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Tyrosine-hydroxylase-containing vagal afferent neurons in the rat Nodose Ganglion are independent from neuropeptide-Y-containing populations and project to esophagus and stomach.
Cell and tissue research, 1993Co-Authors: Wolfgang Kummer, Sebastian Bachmann, Winfried Neuhuber, Jörg Hänze, Rudolf E LangAbstract:Immunoreactivity to the rate limiting enzyme of catecholamine synthesis, tyrosine hydroxylase, has been described in the inferior sensory (= Nodose) Ganglion of the vagal nerve in the rat. The aim of the present study was to characterize further this neuronal population. The neurons do not represent displaced autonomic efferent neurons, since they do not receive synaptic input, as indicated by the absence of synaptophysin-immunoreactive terminals. In addition to the immunoreactivity to tyrosine hydroxylase, a tyrosine hydroxylase cRNA probe hybridizes with Nodose Ganglion neurons as demonstrated by in situ hybridization and Northern blotting. Many but not all of the tyrosine hydroxylase-immunoreactive neurons are also immunoreactive to the dopamine synthesizing enzyme, aromatic-L-amino-acid-decarboxylase, but lack the noradrenaline-synthesizing enzyme, dopamine-beta-hydroxylase, thus favoring synthesis of dopamine. Neuropeptide Y, which is often colocalized with catecholamines, is also present in a subset of Nodose Ganglion neurons, as indicated by immunohistochemistry, in situ hybridization and Northern blotting. However, double-labeling immunofluorescence has revealed that these two antigens are localized in different cell populations. Retrograde neuronal tracing utilizing fluorescent dyes (Fast blue, Fluoro-gold) combined with tyrosine hydroxylase immunohistochemistry has demonstrated that the esophagus and stomach are peripheral targets of tyrosine-hydroxylase-containing vagal viscero-afferent neurons.
Mamoru Takeda - One of the best experts on this subject based on the ideXlab platform.
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direct inhibition of the transient voltage gated k currents mediates the excitability of tetrodotoxin resistant neonatal rat Nodose Ganglion neurons after ouabain application
European Journal of Pharmacology, 2011Co-Authors: Shigeji Matsumoto, Masayuki Takahashi, Kohsuke Iwasaki, Ryoji Ide, Chikako Saiki, Mamoru TakedaAbstract:The purpose of the present study was to determine the relationship between the responses of transient and sustained K(+) currents, and action potentials to ouabain, and to compare the immunoreactive expression of alpha Na(+)-K(+)-ATPase isoforms (α(1), α(2) and α(3)) in neonatal rat small-diameter Nodose Ganglion neurons. We used perforated patch-clamp techniques. We first confirmed that the neurons (n=20) were insensitive to 0.5 μM tetrodotoxin (TTX). Application of 1 μM ouabain 1) decreased the transient K(+) currents in 60% of neurons and the sustained K(+) currents in 20%, 2) increased voltage-gated transient and sustained K(+) currents in 20% of neurons, and 3) had no effect on transient K(+) currents in 20% of neurons and on sustained K(+) currents in 60%. Thirteen of the neurons were of a rapidly adapting type, and the remaining 7 were of a slowly adapting type. In 6 rapidly adapting type neurons (46%), their activity was not significantly altered by ouabain application, but in 4 rapidly adapting type neurons, the activity increased. In the remaining 3 rapidly adapting type neurons, ouabain application hyperpolarized the resting membrane potential. The slowly adapting type 7 neurons each showed increased activity after 1 μM ouabain application. The α(1) isoform of Na(+)-K(+)-ATPase was identified as the predominant immunoreactive isoforms in small-diameter Nodose Ganglion neurons. These results suggest that the increased activity of small-diameter Nodose Ganglion neurons seen after application of 1 μM ouabain is mediated by direct inhibition of the transient K(+) current.
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Direct inhibition of the transient voltage-gated K(+) currents mediates the excitability of tetrodotoxin-resistant neonatal rat Nodose Ganglion neurons after ouabain application.
European journal of pharmacology, 2011Co-Authors: Shigeji Matsumoto, Masayuki Takahashi, Kohsuke Iwasaki, Ryoji Ide, Chikako Saiki, Mamoru TakedaAbstract:The purpose of the present study was to determine the relationship between the responses of transient and sustained K(+) currents, and action potentials to ouabain, and to compare the immunoreactive expression of alpha Na(+)-K(+)-ATPase isoforms (α(1), α(2) and α(3)) in neonatal rat small-diameter Nodose Ganglion neurons. We used perforated patch-clamp techniques. We first confirmed that the neurons (n=20) were insensitive to 0.5 μM tetrodotoxin (TTX). Application of 1 μM ouabain 1) decreased the transient K(+) currents in 60% of neurons and the sustained K(+) currents in 20%, 2) increased voltage-gated transient and sustained K(+) currents in 20% of neurons, and 3) had no effect on transient K(+) currents in 20% of neurons and on sustained K(+) currents in 60%. Thirteen of the neurons were of a rapidly adapting type, and the remaining 7 were of a slowly adapting type. In 6 rapidly adapting type neurons (46%), their activity was not significantly altered by ouabain application, but in 4 rapidly adapting type neurons, the activity increased. In the remaining 3 rapidly adapting type neurons, ouabain application hyperpolarized the resting membrane potential. The slowly adapting type 7 neurons each showed increased activity after 1 μM ouabain application. The α(1) isoform of Na(+)-K(+)-ATPase was identified as the predominant immunoreactive isoforms in small-diameter Nodose Ganglion neurons. These results suggest that the increased activity of small-diameter Nodose Ganglion neurons seen after application of 1 μM ouabain is mediated by direct inhibition of the transient K(+) current.