The Experts below are selected from a list of 21 Experts worldwide ranked by ideXlab platform
Carolyn A. Gilbert - One of the best experts on this subject based on the ideXlab platform.
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Activation of TRPV4 Regulates Respiration through Indirect Activation of Bronchopulmonary Sensory Neurons.
Frontiers in physiology, 2016Co-Authors: Charles R. Moss, Kristen L Kettelhut, Carolyn A. GilbertAbstract:Transient Receptor potential Vanilloid Receptor 4 (TRPV4) is a calcium-permeable non-selective cation channel implicated in numerous physiological and pathological functions. This study aimed to investigate the effect of TRPV4 activation on respiration and to explore the potential involvement of bronchopulmonary sensory neurons. Potent TRPV4 agonist GSK1016790A was injected into right atrium in anesthetized spontaneously breathing rats and the changes in breathing were measured. Patch-clamp recording was performed to investigate the effect of GSK1016790A or another TRPV4 activator 4α-PDD on cultured rat vagal bronchopulmonary sensory neurons. Immunohistochemistry was carried out to determine the TRPV4-expressing cells in lung slices obtained from TRPV4-EGFP mice. Our results showed, that right-atrial injection of GSK1016790A evoked a slow-developing, long-lasting rapid shallow breathing in anesthetized rats. Activation of TRPV4 also significantly potentiated capsaicin-evoked chemoreflex responses. The alteration in ventilation induced by GSK1016790A was abolished by cutting or perineural capsaicin treatment of both vagi, indicating the involvement of bronchopulmonary afferent neurons. The stimulating and sensitizing effects of GSK1016790A were abolished by a selective TRPV4 antagonist GSK2193874 and also by inhibiting cyclooxygenase with indomethacin. Surprising, GSK1016790A or 4α-PDD did not activate isolated bronchopulmonary sensory neurons, nor did they modulate capsaicin-induced inward currents in these neurons. Furthermore, TRPV4 expression was found in alveolar macrophages, alveolar epithelial, and vascular endothelial cells. Collectively, our results suggest that GSK1016790A regulates the respiration through an indirect activation of bronchopulmonary sensory neurons, likely via its stimulation of other TRPV4-expressing cells in the lungs and airways.
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TRPV4 Agonist GSK1016790A Regulates Respiration through Indirect Activation of Bronchopulmonary Sensory Neurons
The FASEB Journal, 2015Co-Authors: Charles R. Moss, Kristen L Kettelhut, Carolyn A. GilbertAbstract:Transient Receptor potential Vanilloid Receptor 4 (TRPV4) is a calcium-permeable non-selective cation channel that has recently been implicated in numerous physiological functions. In this study, w...
Charles R. Moss - One of the best experts on this subject based on the ideXlab platform.
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Activation of TRPV4 Regulates Respiration through Indirect Activation of Bronchopulmonary Sensory Neurons.
Frontiers in physiology, 2016Co-Authors: Charles R. Moss, Kristen L Kettelhut, Carolyn A. GilbertAbstract:Transient Receptor potential Vanilloid Receptor 4 (TRPV4) is a calcium-permeable non-selective cation channel implicated in numerous physiological and pathological functions. This study aimed to investigate the effect of TRPV4 activation on respiration and to explore the potential involvement of bronchopulmonary sensory neurons. Potent TRPV4 agonist GSK1016790A was injected into right atrium in anesthetized spontaneously breathing rats and the changes in breathing were measured. Patch-clamp recording was performed to investigate the effect of GSK1016790A or another TRPV4 activator 4α-PDD on cultured rat vagal bronchopulmonary sensory neurons. Immunohistochemistry was carried out to determine the TRPV4-expressing cells in lung slices obtained from TRPV4-EGFP mice. Our results showed, that right-atrial injection of GSK1016790A evoked a slow-developing, long-lasting rapid shallow breathing in anesthetized rats. Activation of TRPV4 also significantly potentiated capsaicin-evoked chemoreflex responses. The alteration in ventilation induced by GSK1016790A was abolished by cutting or perineural capsaicin treatment of both vagi, indicating the involvement of bronchopulmonary afferent neurons. The stimulating and sensitizing effects of GSK1016790A were abolished by a selective TRPV4 antagonist GSK2193874 and also by inhibiting cyclooxygenase with indomethacin. Surprising, GSK1016790A or 4α-PDD did not activate isolated bronchopulmonary sensory neurons, nor did they modulate capsaicin-induced inward currents in these neurons. Furthermore, TRPV4 expression was found in alveolar macrophages, alveolar epithelial, and vascular endothelial cells. Collectively, our results suggest that GSK1016790A regulates the respiration through an indirect activation of bronchopulmonary sensory neurons, likely via its stimulation of other TRPV4-expressing cells in the lungs and airways.
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TRPV4 Agonist GSK1016790A Regulates Respiration through Indirect Activation of Bronchopulmonary Sensory Neurons
The FASEB Journal, 2015Co-Authors: Charles R. Moss, Kristen L Kettelhut, Carolyn A. GilbertAbstract:Transient Receptor potential Vanilloid Receptor 4 (TRPV4) is a calcium-permeable non-selective cation channel that has recently been implicated in numerous physiological functions. In this study, w...
Kristen L Kettelhut - One of the best experts on this subject based on the ideXlab platform.
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Activation of TRPV4 Regulates Respiration through Indirect Activation of Bronchopulmonary Sensory Neurons.
Frontiers in physiology, 2016Co-Authors: Charles R. Moss, Kristen L Kettelhut, Carolyn A. GilbertAbstract:Transient Receptor potential Vanilloid Receptor 4 (TRPV4) is a calcium-permeable non-selective cation channel implicated in numerous physiological and pathological functions. This study aimed to investigate the effect of TRPV4 activation on respiration and to explore the potential involvement of bronchopulmonary sensory neurons. Potent TRPV4 agonist GSK1016790A was injected into right atrium in anesthetized spontaneously breathing rats and the changes in breathing were measured. Patch-clamp recording was performed to investigate the effect of GSK1016790A or another TRPV4 activator 4α-PDD on cultured rat vagal bronchopulmonary sensory neurons. Immunohistochemistry was carried out to determine the TRPV4-expressing cells in lung slices obtained from TRPV4-EGFP mice. Our results showed, that right-atrial injection of GSK1016790A evoked a slow-developing, long-lasting rapid shallow breathing in anesthetized rats. Activation of TRPV4 also significantly potentiated capsaicin-evoked chemoreflex responses. The alteration in ventilation induced by GSK1016790A was abolished by cutting or perineural capsaicin treatment of both vagi, indicating the involvement of bronchopulmonary afferent neurons. The stimulating and sensitizing effects of GSK1016790A were abolished by a selective TRPV4 antagonist GSK2193874 and also by inhibiting cyclooxygenase with indomethacin. Surprising, GSK1016790A or 4α-PDD did not activate isolated bronchopulmonary sensory neurons, nor did they modulate capsaicin-induced inward currents in these neurons. Furthermore, TRPV4 expression was found in alveolar macrophages, alveolar epithelial, and vascular endothelial cells. Collectively, our results suggest that GSK1016790A regulates the respiration through an indirect activation of bronchopulmonary sensory neurons, likely via its stimulation of other TRPV4-expressing cells in the lungs and airways.
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TRPV4 Agonist GSK1016790A Regulates Respiration through Indirect Activation of Bronchopulmonary Sensory Neurons
The FASEB Journal, 2015Co-Authors: Charles R. Moss, Kristen L Kettelhut, Carolyn A. GilbertAbstract:Transient Receptor potential Vanilloid Receptor 4 (TRPV4) is a calcium-permeable non-selective cation channel that has recently been implicated in numerous physiological functions. In this study, w...
Hui Yang - One of the best experts on this subject based on the ideXlab platform.
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Increased Expression of Transient Receptor Potential Vanilloid 4 in Cortical Lesions of Patients with Focal Cortical Dysplasia.
CNS neuroscience & therapeutics, 2016Co-Authors: Xin Chen, Fei-ji Sun, Yu-jia Wei, Lukang Wang, Zhenle Zang, Bing Chen, Shi-yong Liu, Hui YangAbstract:Summary Aim Focal cortical dysplasia (FCD) represents a well-known cause of medically intractable epilepsy. Studies found that transient Receptor potential Vanilloid Receptor 4 (TRPV4) may participate in the occurrence of seizures. This study investigated the expression patterns of TRPV4 in FCD and the cascade that regulate functional state of TRPV4 in cortical neurons. Methods Thirty-nine surgical specimens from FCD patients and 10 age-matched control samples from autopsies were included in this study. Protein expression and distribution were detected by Western blot, immunohistochemistry, and immunofluorescence staining. Calcium imaging was used to detect the TRPV4-mediated Ca2+ influx in cortical neurons. Results (1) The protein levels of TRPV4 and of an upstream factor, protein kinase C (PKC), were markedly elevated in FCD. (2) TRPV4 staining was stronger in the dysplastic cortices of FCD and mainly observed in neuronal microcolumns and malformed cells. (3) The activation of TRPV4 was central for [Ca2+]i elevation in cortical neurons, and this activity of TRPV4 in cortical neurons was regulated by the PKC, but not the PKA, pathway. Conclusion The overexpression and altered cellular distribution of TRPV4 in FCD suggest that TRPV4 may potentially contribute to the epileptogenesis of FCD.
Xin Chen - One of the best experts on this subject based on the ideXlab platform.
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Increased Expression of Transient Receptor Potential Vanilloid 4 in Cortical Lesions of Patients with Focal Cortical Dysplasia.
CNS neuroscience & therapeutics, 2016Co-Authors: Xin Chen, Fei-ji Sun, Yu-jia Wei, Lukang Wang, Zhenle Zang, Bing Chen, Shi-yong Liu, Hui YangAbstract:Summary Aim Focal cortical dysplasia (FCD) represents a well-known cause of medically intractable epilepsy. Studies found that transient Receptor potential Vanilloid Receptor 4 (TRPV4) may participate in the occurrence of seizures. This study investigated the expression patterns of TRPV4 in FCD and the cascade that regulate functional state of TRPV4 in cortical neurons. Methods Thirty-nine surgical specimens from FCD patients and 10 age-matched control samples from autopsies were included in this study. Protein expression and distribution were detected by Western blot, immunohistochemistry, and immunofluorescence staining. Calcium imaging was used to detect the TRPV4-mediated Ca2+ influx in cortical neurons. Results (1) The protein levels of TRPV4 and of an upstream factor, protein kinase C (PKC), were markedly elevated in FCD. (2) TRPV4 staining was stronger in the dysplastic cortices of FCD and mainly observed in neuronal microcolumns and malformed cells. (3) The activation of TRPV4 was central for [Ca2+]i elevation in cortical neurons, and this activity of TRPV4 in cortical neurons was regulated by the PKC, but not the PKA, pathway. Conclusion The overexpression and altered cellular distribution of TRPV4 in FCD suggest that TRPV4 may potentially contribute to the epileptogenesis of FCD.
