We have studied the modulation of gating properties of the Ca2+-permeable, cation channel TRPV4 transiently expressed in HEK293 cells. The phorbol ester 4αPDD transiently activated a current through TRPV4 in the presence of extracellular Ca2+. Increasing the concentration of extracellular Ca2+ ([Ca2+]e) reduced the current amplitude and accelerated its decay. This decay was dramatically delayed in the absence of [Ca2+]e. It was also much slower in the presence of [Ca2+]e in a mutant channel, obtained by a point mutation in the 6th transmembrane domain, F707A. Mutant channels, containing a single mutation in the C-terminus of TRPV4 (E797 , were constitutively open. In conclusion, gating of the 4αPDD-activated TRPV4 channel depends on both extra- and intracellular Ca2+, and is modulated by mutations of single amino acid residues in the 6th transmembrane domain and the C-terminus of the TRPV4 protein.

Many endothelial cell (EC) functions depend on influx of extracellular Ca2+, which is triggered by a variety of mechanical and chemical signals. Here, we discuss possible pathways for this Ca2+ entry. The superfamily of cation channels derived from the "transient receptor potential" (TRP) channels is introduced. Several members of this family are expressed in ECs, and they provide pathways for Ca2+ entry. All TRP subfamilies may contribute to the Ca2+ entry channels or to the regulation of Ca2+ entry in EC. Members of Ca2+ entry channels in endothelium probably belong to the canonical TRP subfamily, TRPC. All TRPC1-6 have been discussed as Ca2+ entry channels that might be store-operated and/or receptor-operated. More importantly, knockout models of TRPC4 have proven that this channel is functionally involved in the regulation of endothelial-dependent vasorelaxation and in the control of EC barrier function. TRPC1 might be an important candidate for involvement of eodothelial growth factors. TRPC3 is unequivocally important for a sustained EC Ca2+ entry. ECs express different patterns of TRPCs, which may increase the variability of TRPC channel function by formation of different multiheteromers. Among the two other TRP subfamilies, TRPMV and TRPM, at least TRPV4 and TRPM4 are EC channels. TRPV4 is a Ca2+ entry channel that is activated by an increase in cell volume, which might be involved in mechano-sensing, by an increase in temperature, and perhaps by ligand-activation. TRPM4 is a nonselective cation channel, which is not Ca2+ permeable. It is probably modulated by NO and might be essential for regulating the inward driving force for Ca2+ entry. Possible modes of TRP channel regulation are described, involving (a) activation via the phospholipase (PL)Cβ and PLCγ pathways; (b) activation by lipids (diacylglycerol [DAG], arachidonic acid); (c) Ca2+ depletion of Ca2+ stores in the endoplasmic reticulum; (d) shear stress; and (e) radicals.

No description available.

No description available.

Introdução. A hiperativação nervosa simpática é característica marcante da insuficiência cardíaca. Estudos apontam alterações no controle ergorreflexo muscular (mecano e metaborreflexo) como mecanismos potenciais para explicar esta modificação autonômica. Os mecanorreceptores (fibras do grupo III), que são ativadas pelo aumento no tônus muscular e modulados por metabólitos da via das ciclooxigenases, encontram-se hipersensibilizadas na insuficiência cardíaca. Ao contrário, a sensibilidade dos metaborreceptores (fibras do grupo IV), que são ativados pelo acúmulo de metabólitos durante as contrações musculares e modulados pelos receptores TRPV1 e CB1, encontra-se diminuída na insuficiência cardíaca. Por outro lado, o treinamento físico tem se mostrado uma importante ferramenta no tratamento da insuficiência cardíaca. Ele reduz os níveis de atividade nervosa simpática muscular (ANSM) no repouso e durante o exercício em pacientes portadores desta síndrome. Dessa forma, neste estudo, nós testamos a hipótese de que o treinamento físico melhoraria o controle mecano e metaborreflexo da ANSM em pacientes com insuficiência cardíaca, e se essa melhora está associada às alterações na via das ciclooxigenases e na expressão dos receptores TRPV1 e CB1, respectivamente. Métodos. Pacientes com insuficiência cardíaca foram consecutivamente e aleatoriamente divididos em dois grupos: insuficiência cardíaca não treinado (ICNT, n=17) e insuficiência cardíaca treinado (ICT, n=17). A ANSM foi avaliada pela técnica de microneurografia e o fluxo sanguíneo muscular (FSM) pela pletismografia de oclusão venosa. A frequência cardíaca (FC) e a pressão arterial (PA) foram avaliadas por medida não invasiva a cada batimento (Finometer). Foi realizada biopsia muscular do vasto lateral para análise de expressão gênica. O treinamento físico aeróbio foi realizado em ciclo ergômetro, em intensidade moderada, por 40 minutos, três vezes por semana, durante 16 semanas. A sensibilidade mecanorreflexa foi calculada pelo delta absoluto entre o pico do exercício passivo, realizado na perna esquerda, e a média do registro basal. A sensibilidade metaborreflexa foi calculada pelo delta absoluto entre o 1º minuto de oclusão circulatória pós-exercício na perna esquerda e a média do registro basal. Resultados. O treinamento físico reduziu a ANSM e aumentou o FSM no repouso. O treinamento físico diminuiu significativamente as respostas de ANSM durante o exercício passivo no grupo ICT. As repostas de PA média também foram menores no grupo ICT quando comparado ao grupo ICNT. Não houve alterações significativas nas repostas de FC, PA sistólica, PA diastólica e FSM durante o exercício passivo no grupo ICT. Em relação à sensibilidade metaborreflexa, o treinamento físico aumentou expressivamente as respostas de ANSM no 1º minuto de oclusão circulatória no grupo ICT. As respostas de FC, PA e FSM não foram alteradas neste grupo. Não foram observadas alterações significativas nos controles mecano e metaborreflexo musculares no grupo ICNT. Além disso, o treinamento físico reduziu significativamente a expressão gênica da enzima COX-2 e do receptor EP4 e aumentou significativamente a expressão dos receptores TRPV1 e CB1 no grupo ICT. Não foram verificadas alterações significativas nas expressões gênicas do grupo ICNT. Conclusões. O treinamento físico normaliza os controles mecano e metaborreflexo da ANSM em pacientes com insuficiência cardíaca. Estas alterações podem estar associadas às alterações na expressão gênica da enzima COX-2 e receptor EP4, e dos receptores TRPV1 e CB1, respectivamente. Em conjunto, estes achados podem explicar, pelo menos em parte, a diminuição da atividade nervosa simpática e a melhora na tolerância aos esforços em pacientes com insuficiência cardíaca / Introduction. Sympathoexcitation is the hallmark of heart failure. Studies suggest changes in ergoreflex muscle control (mechanoreflex and metaboreflex) as potential mechanisms to explain this autonomic alteration in heart failure. Mechanoreceptors (group III fibers) that are activated by mechanical stimuli and modulated by cyclooxygenase pathway metabolites are hypersensitive in heart failure. In contrast, the sensitivity of metaboreceptors fibers (group IV) that are activated by increases in ischemic metabolites during muscle contractions and modulated by TRPV1 and CB1 receptors is blunted in heart failure. On the other hands, exercise training has been shown to be an important strategy in the treatment of heart failure. It reduces the levels of muscle sympathetic nerve activity (MSNA) at rest and during exercise in patients suffering of this syndrome. Thus, we tested the hypothesis that exercise training would improve the mechanoreflex and metaboreflex control of MSNA in heart failure patients. In addition, we investigated whether the improvement in the mechanoreflex and metaboreflex control is related to changes in the cyclooxygenase pathway and expression of TRPV1 and CB1 receptors, respectively. Methods. Patients with heart failure were consecutively and randomly divided into two groups: heart failure untrained (HFUT, n = 17) and heart failure exercise-trained (HFET, n = 17). MSNA was measured by microneurography technique and muscle blood flow (MBF) by venous occlusion plethysmography. Heart rate (HR) and blood pressure (BP) were assessed by noninvasive measure on a beat-to-beat basis (Finometer). Gene expression analysis was investigated by vastus lateralis muscle biopsy. Aerobic exercise training was performed on a cycle ergometer at moderate intensity, three 40-min session/wk for 16 weeks. Mechanoreflex sensitivity was evaluated by means the absolute difference in MSNA at peak passive exercise and baseline. Metaboreflex sensitivity was calculated by means the absolute difference in MSNA at 1st min after exercise period with muscle circulatory arrest and baseline. Results. Exercise training reduced MSNA and increased MBF. Exercise training significantly decreased MSNA responses during passive exercise. The mean BP response was lower in HFET group when compared to HFUT group. There were no significant changes in HR, systolic and diastolic BP and MBF responses during passive exercise in HFET group. Regarding metaboreflex sensitivity, exercise training significantly increased the MSNA responses at 1st minute of post exercise circulatory arrest. The responses of HR, BP and MBF were unchanged after exercise training. No significant changes were observed in mechanoreflex and metaboreflex control in the HFUT group. Furthermore, exercise training significantly reduced gene expression of COX-2 and EP4 receptor and significantly increased expression of TRPV1 and CB1 receptors. There were no significant changes in the gene expressions in the HFUT group. Conclusions. Exercise training improves mechanoreflex and metaboreflex control of MSNA in heart failure patients. These changes may be associated with changes in gene expression of COX-2 and EP4 receptor and TRPV1 and CB1 receptor, respectively. Together, these findings may explain, at least in part, the decrease in sympathetic nerve activity and the improvement in exercise tolerance in patients with heart failure

Introdução. A hiperativação nervosa simpática é característica marcante da insuficiência cardíaca. Estudos apontam alterações no controle ergorreflexo muscular (mecano e metaborreflexo) como mecanismos potenciais para explicar esta modificação autonômica. Os mecanorreceptores (fibras do grupo III), que são ativadas pelo aumento no tônus muscular e modulados por metabólitos da via das ciclooxigenases, encontram-se hipersensibilizadas na insuficiência cardíaca. Ao contrário, a sensibilidade dos metaborreceptores (fibras do grupo IV), que são ativados pelo acúmulo de metabólitos durante as contrações musculares e modulados pelos receptores TRPV1 e CB1, encontra-se diminuída na insuficiência cardíaca. Por outro lado, o treinamento físico tem se mostrado uma importante ferramenta no tratamento da insuficiência cardíaca. Ele reduz os níveis de atividade nervosa simpática muscular (ANSM) no repouso e durante o exercício em pacientes portadores desta síndrome. Dessa forma, neste estudo, nós testamos a hipótese de que o treinamento físico melhoraria o controle mecano e metaborreflexo da ANSM em pacientes com insuficiência cardíaca, e se essa melhora está associada às alterações na via das ciclooxigenases e na expressão dos receptores TRPV1 e CB1, respectivamente. Métodos. Pacientes com insuficiência cardíaca foram consecutivamente e aleatoriamente divididos em dois grupos: insuficiência cardíaca não treinado (ICNT, n=17) e insuficiência cardíaca treinado (ICT, n=17). A ANSM foi avaliada pela técnica de microneurografia e o fluxo sanguíneo muscular (FSM) pela pletismografia de oclusão venosa. A frequência cardíaca (FC) e a pressão arterial (PA) foram avaliadas por medida não invasiva a cada batimento (Finometer). Foi realizada biopsia muscular do vasto lateral para análise de expressão gênica. O treinamento físico aeróbio foi realizado em ciclo ergômetro, em intensidade moderada, por 40 minutos, três vezes por semana, durante 16 semanas. A sensibilidade mecanorreflexa foi calculada pelo delta absoluto entre o pico do exercício passivo, realizado na perna esquerda, e a média do registro basal. A sensibilidade metaborreflexa foi calculada pelo delta absoluto entre o 1º minuto de oclusão circulatória pós-exercício na perna esquerda e a média do registro basal. Resultados. O treinamento físico reduziu a ANSM e aumentou o FSM no repouso. O treinamento físico diminuiu significativamente as respostas de ANSM durante o exercício passivo no grupo ICT. As repostas de PA média também foram menores no grupo ICT quando comparado ao grupo ICNT. Não houve alterações significativas nas repostas de FC, PA sistólica, PA diastólica e FSM durante o exercício passivo no grupo ICT. Em relação à sensibilidade metaborreflexa, o treinamento físico aumentou expressivamente as respostas de ANSM no 1º minuto de oclusão circulatória no grupo ICT. As respostas de FC, PA e FSM não foram alteradas neste grupo. Não foram observadas alterações significativas nos controles mecano e metaborreflexo musculares no grupo ICNT. Além disso, o treinamento físico reduziu significativamente a expressão gênica da enzima COX-2 e do receptor EP4 e aumentou significativamente a expressão dos receptores TRPV1 e CB1 no grupo ICT. Não foram verificadas alterações significativas nas expressões gênicas do grupo ICNT. Conclusões. O treinamento físico normaliza os controles mecano e metaborreflexo da ANSM em pacientes com insuficiência cardíaca. Estas alterações podem estar associadas às alterações na expressão gênica da enzima COX-2 e receptor EP4, e dos receptores TRPV1 e CB1, respectivamente. Em conjunto, estes achados podem explicar, pelo menos em parte, a diminuição da atividade nervosa simpática e a melhora na tolerância aos esforços em pacientes com insuficiência cardíaca / Introduction. Sympathoexcitation is the hallmark of heart failure. Studies suggest changes in ergoreflex muscle control (mechanoreflex and metaboreflex) as potential mechanisms to explain this autonomic alteration in heart failure. Mechanoreceptors (group III fibers) that are activated by mechanical stimuli and modulated by cyclooxygenase pathway metabolites are hypersensitive in heart failure. In contrast, the sensitivity of metaboreceptors fibers (group IV) that are activated by increases in ischemic metabolites during muscle contractions and modulated by TRPV1 and CB1 receptors is blunted in heart failure. On the other hands, exercise training has been shown to be an important strategy in the treatment of heart failure. It reduces the levels of muscle sympathetic nerve activity (MSNA) at rest and during exercise in patients suffering of this syndrome. Thus, we tested the hypothesis that exercise training would improve the mechanoreflex and metaboreflex control of MSNA in heart failure patients. In addition, we investigated whether the improvement in the mechanoreflex and metaboreflex control is related to changes in the cyclooxygenase pathway and expression of TRPV1 and CB1 receptors, respectively. Methods. Patients with heart failure were consecutively and randomly divided into two groups: heart failure untrained (HFUT, n = 17) and heart failure exercise-trained (HFET, n = 17). MSNA was measured by microneurography technique and muscle blood flow (MBF) by venous occlusion plethysmography. Heart rate (HR) and blood pressure (BP) were assessed by noninvasive measure on a beat-to-beat basis (Finometer). Gene expression analysis was investigated by vastus lateralis muscle biopsy. Aerobic exercise training was performed on a cycle ergometer at moderate intensity, three 40-min session/wk for 16 weeks. Mechanoreflex sensitivity was evaluated by means the absolute difference in MSNA at peak passive exercise and baseline. Metaboreflex sensitivity was calculated by means the absolute difference in MSNA at 1st min after exercise period with muscle circulatory arrest and baseline. Results. Exercise training reduced MSNA and increased MBF. Exercise training significantly decreased MSNA responses during passive exercise. The mean BP response was lower in HFET group when compared to HFUT group. There were no significant changes in HR, systolic and diastolic BP and MBF responses during passive exercise in HFET group. Regarding metaboreflex sensitivity, exercise training significantly increased the MSNA responses at 1st minute of post exercise circulatory arrest. The responses of HR, BP and MBF were unchanged after exercise training. No significant changes were observed in mechanoreflex and metaboreflex control in the HFUT group. Furthermore, exercise training significantly reduced gene expression of COX-2 and EP4 receptor and significantly increased expression of TRPV1 and CB1 receptors. There were no significant changes in the gene expressions in the HFUT group. Conclusions. Exercise training improves mechanoreflex and metaboreflex control of MSNA in heart failure patients. These changes may be associated with changes in gene expression of COX-2 and EP4 receptor and TRPV1 and CB1 receptor, respectively. Together, these findings may explain, at least in part, the decrease in sympathetic nerve activity and the improvement in exercise tolerance in patients with heart failure

Introdução: Receptores TRPV1 são canais catiônicos nociceptivos não seletivos. Eles desempenham um papel na sensação de dor na córnea. No presente trabalho, descreveremos a resposta do TRPV1 na córnea de camundongos e TRPV1 -/- a estímulos químicos e o efeito do SNAP sobre este receptor. Métodos: camundongos C57BL/6 e TRPV1 -/- foram comparados. As observações incluíram o influxo de cálcio na cultura, observação direta e o comportamento de limpeza do olho após o desafio na córnea com 1µM da capsaicina (CAP) com ou sem 1mM do colírio SNAP. Resultados: As características da superfície ocular não eram diferentes entre ambos os genótipos, exceto que a sensibilidade para CAP é inferior em TRPV1 -/- (p = 0,0019 e 0,0095, respectivamente). A imunocoloração revelou que TRPV1 é expresso na camada basal do epitélio da córnea, apenas nos camundongos C57BL/6. CAP estimula o influxo de cálcio em cultura de células epiteliais e a sensibilidade corneana em C57BL/6 in vivo foi reduzida na presença do SNAP (p = 0,0329 e 0,01, respectivamente). Conclusão: A ausência dos receptores TRPV1 no epitélio da córnea não afeta o fenótipo da superfície ocular de camundongos. A resposta para tirar colírios revelou que ela poderia funcionar como uma terapia analgésica devido ao seu antagonismo com o TRPV1. / TRPV-1 receptors are non-selective nocioceptive cation channels. They play a role in cornea sensation. In the present work we describe the response of corneas of TRPV1-/- and mice to chemical stimuli and the effect of SNAP on this receptor. TRPV1-/- and C57BL/6 mice were compared. The observations included the calcium influx in culture, direct observation and the behavior of eye wipe after corneal challenge with 1?M Capsaicin (CAP) with or not 1mM SNAP eye drops. Ocular surface characteristics were not different between both genotypes, except that the sensitivity to CAP is lower in TRPV1-/- (p=0.0019 and 0.0095, respectively). Immunostaining revealed that TRPV 1 is expressed in the basal layer of the cornea epithelia, only in the C57 mice. CAP stimulated calcium influx in epithelial cells in culture and cornea sensitivity in C57 mice in vivo was reduced in the presence of SNAP (p=0.0329 and 0.01, respectively). The absence of TRPV-1 receptors in the cornea epithelia did not affect the ocular surface phenotype in mice. The response to SNAP eye drops revealed that it could work as an analgesic therapy due to its antagonism to the TRPV1.

Introdução: Receptores TRPV1 são canais catiônicos nociceptivos não seletivos. Eles desempenham um papel na sensação de dor na córnea. No presente trabalho, descreveremos a resposta do TRPV1 na córnea de camundongos e TRPV1 -/- a estímulos químicos e o efeito do SNAP sobre este receptor. Métodos: camundongos C57BL/6 e TRPV1 -/- foram comparados. As observações incluíram o influxo de cálcio na cultura, observação direta e o comportamento de limpeza do olho após o desafio na córnea com 1µM da capsaicina (CAP) com ou sem 1mM do colírio SNAP. Resultados: As características da superfície ocular não eram diferentes entre ambos os genótipos, exceto que a sensibilidade para CAP é inferior em TRPV1 -/- (p = 0,0019 e 0,0095, respectivamente). A imunocoloração revelou que TRPV1 é expresso na camada basal do epitélio da córnea, apenas nos camundongos C57BL/6. CAP estimula o influxo de cálcio em cultura de células epiteliais e a sensibilidade corneana em C57BL/6 in vivo foi reduzida na presença do SNAP (p = 0,0329 e 0,01, respectivamente). Conclusão: A ausência dos receptores TRPV1 no epitélio da córnea não afeta o fenótipo da superfície ocular de camundongos. A resposta para tirar colírios revelou que ela poderia funcionar como uma terapia analgésica devido ao seu antagonismo com o TRPV1. / TRPV-1 receptors are non-selective nocioceptive cation channels. They play a role in cornea sensation. In the present work we describe the response of corneas of TRPV1-/- and mice to chemical stimuli and the effect of SNAP on this receptor. TRPV1-/- and C57BL/6 mice were compared. The observations included the calcium influx in culture, direct observation and the behavior of eye wipe after corneal challenge with 1?M Capsaicin (CAP) with or not 1mM SNAP eye drops. Ocular surface characteristics were not different between both genotypes, except that the sensitivity to CAP is lower in TRPV1-/- (p=0.0019 and 0.0095, respectively). Immunostaining revealed that TRPV 1 is expressed in the basal layer of the cornea epithelia, only in the C57 mice. CAP stimulated calcium influx in epithelial cells in culture and cornea sensitivity in C57 mice in vivo was reduced in the presence of SNAP (p=0.0329 and 0.01, respectively). The absence of TRPV-1 receptors in the cornea epithelia did not affect the ocular surface phenotype in mice. The response to SNAP eye drops revealed that it could work as an analgesic therapy due to its antagonism to the TRPV1.

Attempts were made to determine the pore properties, such as permeability, rectification and voltage-dependent block, of the putative TRPV4-TRPC1 channel. We demonstrated that this putative TRPV4-TRPC1 heterotetrameric channels displays distinct property different (although not drastically different) from TRPV4 homotetrameric channel with regard to I-V relation, kinetics of cation current, cations permeability and rectification properties. Together, the data from FRET and functional studies both suggest that heterologous expression of TRPV4 and TRPC1 can produce functional TRPV4-TRPC1 heterotetrameric channel. / Hemodynamic blood flow is one of most important physiological factors that control vascular tone. Flow shear stress acts on the endothelium to stimulate the release of vasodilators such as nitric oxide (NO), prostacyclin and endothelium-derived hyperpolarizing factors, causing endothelium-dependent vascular relaxation. In many cases, a key early signal in this flow-induced vascular dilation is Ca2+ influx in endothelial cells in response to flow. There is intense interest in searching for the molecular identity of the channels that mediate flow-induced Ca2+ influx. The present study aimed at identifying an interaction of TRPV4 with TRPC1, and investigating functional role of such a complex in flow-induced Ca2+ influx / In functional study, flow elicited a [Ca2+]i rise in TRPV4-expressing HEK cells. Co-expression of TRPC1 with TRPV4 markedly prolonged this [Ca2+]i transient, and it also enabled this [Ca2+]i transient to be negatively modulated by protein kinase G (PKG). Furthermore, this [Ca2+]i rise was inhibited by an anti-TRPC1 blocking antibody T1E3 and a dominant negative construct TRPC1Delta567-793. Physical interaction of TRPV4 with TRPC1 and functional role of such a complex were also found in the primary cultured rat mesenteric artery endothelial cells (MAECs) and human umbilical vein endothelial cells (HUVECs). A TRPC 1-specific siRNA was used to knock-down TRPC1 protein levels in HUVECs. Interestingly, this siRNA not only reduced the magnitude of flow-induced [Ca2+]i rise, but also accelerated the decay of flow-induced [Ca2+]i transient. Pressure myograph was used to investigate the functional role of such a complex in flow-induced vascular dilation. T1E3 also decreased flow-induced vascular dilation. Thogether, the data from endothelial cells are consistent with those in overexpressed HEK cells, supporting the notion that TRPC 1 interacts with TRPV4 to prolong the flow-induced[Ca2+]i transient, and that TRPV4-TRPC1 complex plays an important role in flow-induced vascular dilation. / In summary, my study demonstrated that TRPV4 is capable of assembling with TRPC1 to form a functional TRPV4-TRPC1 heteromeric channel. TRPV4-TRPC1 heteromeric channel can rapidly translocate to the plasma membrane after Ca 2+ depletion in intracellular stores. This TRPV4-TRPC1 heteromeric channel plays an important role in flow-induced endothelial Ca2+ influx and its associated vascular relaxation. / Ion channels are delivered to the plasma membrane via vesicle trafficking. Thus the vesicle trafficking is a key mechanism to control the amount of TRP channel proteins in the plasma membrane, where they perform their function. TRP channels in vivo are often composed of heteromeric subunits. However, up to the present, there is lack of knowledge on trafficking of heteromeric TRP channels via vesicular translocation. In the present study, we examined the effect of Ca2+ store depletion on the translocation of TRPV4-TRPC1 heteromeric channels to the plasma membrane. Experiments using total internal fluorescence reflection microscopy (TIRFM) and biotin surface labeling showed that depletion of intracellular Ca2+ stores triggered a rapid translocation of TRPV4-TRPC1 channel proteins into the plasma membrane. Fluorescent Ca2+ measurement and patch clamp studies demonstrated that store Ca2+ depletion augmented several TRPV4-TRPC1 complex-related functions, which include store-operated Ca2+ influx and cation current as well as 4alpha-PDD-stimulated Ca2+ influx and cation current. The translocation required stromal interacting molecule 1 (STIM1). Furthermore, TRPV4-TRPC1 complex is more favorably translocated to the plasma membrane than TRPC1 or TRPV4 homomers. Similar mechanisms were identified in native endothelial cells, where the TRPV4-TRPC I complex is a key component mediating flow-induced Ca2+ influx and subsequent vascular relaxation. / With the use of fluorescence resonance energy transfer (FRET), co-immunoprecipitation and subcellular colocalization methods, it was found that TRPC1 interacts physically with TRPV4 to form a heteromeric channel complex. In addition, our experimental results indicate that C-terminal and N-terminal domains of both channels are required for their interaction. / Ma, Xin. / Adviser: Yao Xiaodiang. / Source: Dissertation Abstracts International, Volume: 72-04, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 109-121). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

No description available.