Acta Physiol 2015, 214, 6–7
ExActa TRPs revisited Perception of potentially harmful or toxic environmental stimuli is critical for survival of, but not only, highly differentiated organisms. Transient receptor potential (TRP) channels are mostly membrane receptors, located on an extensive array of animal cells from a wide variety of species. More than 45 years ago, Derek Cosens and Aubrey Manning reported to have created a ‘mutant strain of Drosophila melanogaster which, though behaving phototactically positive in a T-maze under low ambient light, is visually impaired and behaves as though blind in a simple optomotor apparatus where normal, wild-type flies will orientate to visual cues’ (Cosens & Manning 1969). Loss of TRP in D. melanogaster results in a transient response (therefore the name) to light, while physiologically, D. melanogaster light response shows sustained photoreceptor cell activity. To date, seven subfamilies have been described, including transient receptor potential canonical (TRPC), transient receptor potential vanilloid (TRPV), transient receptor potential melastatin (TRPM), transient receptor potential polycystin (TRPP), transient receptor potential mucolipin (TRPML), transient receptor potential ankyrin (TRPA) and transient receptor potential ‘No mechanoreceptor potential C’like (TRPN). Apart from TRPN, expressed in invertebrates and fish, most TRP channels may be found throughout the body of numerous species including man (Nilius & Owsianik 2011). Structurally, the subfamilies resemble one another, with mostly six membrane-spanning helices and intracellularly located Cand N-termini. Their function is often sensory in nature. In addition to their role in vision described above, TRP channels are activated in response to stimuli such as high or low temperature or mechanical stimulation. Involvement of TRP channels in taste reception is to some degree debatable. This assumption may be based on the role of polymodal nociceptors in generating the ‘false’ perception of heat or cold by agents such as menthol, capsaicin or allyl isothiocyanate (Wasabi). Why is it that in the English language, which, due to its development on the borders of a historical interface of cultures, having developed into the leading language of international exchange and lingua franca (McCrum et al. 2003), with all its Germanic and Latinate synonyms and nuances, one commonly uses the same word for the sensation brought about by biting on a chilli pepper or by sipping from an overheated drink? ‘Hot’ 6
brings about an interesting ambiguity of taste and temperature sensations, which is not necessarily reflected to a similar degree in other Indogermanic word pools. ‘Pungent’, which reflects the ‘hot taste’ (think Wasabi) sensation transmitted to the CNS by polymodal somatosensory fibres, is much more rarely used. Menthol confuses the body even more than Wasabi does, by simultaneously activating hot and cold fibres, an effect cleverly used when marketing, for example the ‘Icy Hot’ products based on a developmental ‘accident in human physiology’ (Green 1999). Pungency is not a taste in the true sense of the word as its perception is not limited to the taste buds (Ever wiped your eyes after slicing a chilli pepper, anyone?) but, however, an integral part of Eastern cuisine. How do the TRPs do it then? Most are non-selective cation (Na/Ca/Mg) channels, few are selective, for example Ca or hydrated Mg ions. TRPs function mostly as triggers of intracellular Ca release. Channel activation depolarizes the membrane, activating voltage-gated channels (Nilius & Owsianik 2011). TRPs – their location on so many different cell types indicates it – are capable of doing much more, and new functions are regularly described. TRPs are required for endosome and lysosome function and critically involved in cell volume control and, thus, for example control of vascular tone and permeability, mechanosensing, secretion, angiogenesis and endothelial cell (EC) activation, proliferation, apoptosis and death (Yao & Garland 2005). Recently, TRPV1 has been described to be involved in simvastatin-mediated eNOS activation (Su et al. 2014) and phosphorylation (Ching et al. 2013), affecting angiogenesis (Usui et al. 2014, Mittal et al. 2015). TRPVs are involved in pathological states of the circulatory system (Yao & Garland 2005, Wei et al. 2013), neurodegenerative disorders, pain syndromes, skeletal dysplasia and pathologies of the urinary system (Nilius & Owsianik 2011). TRPV1 and 4 are involved in kidney failure, their activation affecting the outcome of ischaemic acute kidney injury (Kassmann et al. 2013), no. 1 cause of hospital-acquired mortality (Kusch et al. 2013, Persson 2013, Pohlmann et al. 2013). Most interestingly, they do so via TRPV1 channels in dorsal root ganglion neurones that innervate the kidney. Urinary bladder regulation is another focus of physiological research (de Groat & Wickens 2013, McCloskey 2013), with some recent interesting publications focusing on generation of bladder-related
© 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd, doi: 10.1111/apha.12492
Acta Physiol 2015, 214, 6–7
autonomous (Ochodnicky et al. 2013) and sensory signals (Birder & Wyndaele 2013) and, specifically, the role of TRP channels in bladder function (Avelino et al. 2013, Burnstock 2013) and idiopathic overactive bladder syndromes (Birder et al. 2013). In 2012, Acta Physiologica devoted a special issue to the results of the International Symposium on G protein-coupled receptors, TRP ion channels and lipid signalling. Let’s look forward to more exciting results on the TRP ion channel family to come.
Conflict of interest None.
P. B. Persson Institute of Vegetative Physiology, Charite-Universitaetsmedizin Berlin, Berlin, Germany E-mail: [email protected]
References Avelino, A., Charrua, A., Frias, B., Cruz, C., Boudes, M., de Ridder, D. & Cruz, F. 2013. Transient receptor potential channels in bladder function. Acta Physiol (Oxf) 207, 110–122. Birder, L. & Wyndaele, J.J. 2013. From urothelial signalling to experiencing a sensation related to the urinary bladder. Acta Physiol (Oxf) 207, 34–39. Birder, L.A., Wolf-Johnston, A.S., Sun, Y. & Chai, T.C. 2013. Alteration in TRPV1 and Muscarinic (M3) receptor expression and function in idiopathic overactive bladder urothelial cells. Acta Physiol (Oxf) 207, 123–129. Burnstock, G. 2013. Purinergic signalling in the lower urinary tract. Acta Physiol (Oxf) 207, 40–52. Ching, L.C., Zhao, J.F., Su, K.H., Shyue, S.K., Hsu, C.P., Lu, T.M., Lin, S.J. & Lee, T.S. 2013. Activation of transient receptor potential vanilloid 1 decreases endothelial nitric oxide synthase phosphorylation at Thr497 by protein phosphatase 2B-dependent dephosphorylation of protein kinase C. Acta Physiol (Oxf) 209, 124–135. Cosens, D.J. & Manning, A. 1969. Abnormal electroretinogram from a Drosophila mutant. Nature 1969, 285–287. Green, B. 1999. Why is it that eating spicy, “hot” food causes the same physical reactions as does physical heat? Scientific American [online] Available at: http://www.scientificamerican.com/article/why-is-it-that-eating-spi/ (accessed March 13, 2015). de Groat, W.C. & Wickens, C. 2013. Organization of the neural switching circuitry underlying reflex micturition. Acta Physiol (Oxf) 207, 66–84.
P B Persson
· ExActa
Kassmann, M., Harteneck, C., Zhu, Z., N€ urnberg, B., Tepel, M. & Gollasch, M. 2013. Transient receptor potential vanilloid 1 (TRPV1), TRPV4, and the kidney. Acta Physiol (Oxf) 207, 546–564. Kusch, A., Hoff, U., Bubalo, G., Zhu, Y., Fechner, M., Schmidt-Ullrich, R., Marko, L., M€ uller, D.N., SchmidtOtt, K.M., G€ urgen, D., Blum, M., Schunck, W.H. & Dragun, D. 2013. Novel signalling mechanisms and targets in renal ischaemia and reperfusion injury. Acta Physiol (Oxf) 2013, 25–40. McCloskey, K.D. 2013. Bladder interstitial cells: an updated review of current knowledge. Acta Physiol (Oxf) 207, 7– 15. McCrum, R., MacNeil, R. & Cran, W. 2003. The Story of English, 3rd revised edn. Penguin Books, London. ISBN 978-0-14-200231-5. Mittal, M., Urao, N., Hecquet, C.M., Zhang, M., Sudhahar, V., Gao, X.P., Komarova, Y., Ushio-Fukai, M. & Malik, A.B. 2015. Novel role of reactive oxygen speciesactivated trp melastatin channel-2 in mediating angiogenesis and postischemic neovascularization. Arterioscler Thromb Vasc Biol ATVBAHA.114.304802. [Epub ahead of print]. Nilius, B. & Owsianik, G. 2011. The transient receptor potential family of ion channels. Genome Biol 12, 218. Ochodnicky, P., Uvelius, B., Andersson, K.E. & Michel, M.C. 2013. Autonomic nervous control of the urinary bladder. Acta Physiol (Oxf) 207, 16–33. Persson, P.B. 2013. Mechanisms of acute kidney injury. Acta Physiol (Oxf) 207, 430–431. Pohlmann, A., Cantow, K., Hentschel, J., Arakelyan, K., Ladwig, M., Flemming, B., Hoff, U., Persson, P.B., Seeliger, E. & Niendorf, T. 2013. Linking non-invasive parametric MRI with invasive physiological measurements (MRPHYSIOL): towards a hybrid and integrated approach for investigation of acute kidney injury in rats. Acta Physiol (Oxf) 207, 673–689. Su, K.H., Lin, S.J., Wei, J., Lee, K.I., Zhao, J.F., Shyue, S.K. & Lee, T.S. 2014. The essential role of transient receptor potential vanilloid 1 in simvastatin-induced activation of endothelial nitric oxide synthase and angiogenesis. Acta Physiol (Oxf) 212, 191–204. Usui, T., Naruo, A., Okada, M., Hayabe, Y. & Yamawaki, H. 2014. Brain-derived neurotrophic factor promotes angiogenic tube formation through generation of oxidative stress in human vascular endothelial cells. Acta Physiol (Oxf) 211, 385–394. Wei, J., Ching, L.C., Zhao, J.F., Shyue, S.K., Lee, H.F., Kou, Y.R. & Lee, T.S. 2013. Essential role of transient receptor potential vanilloid type 1 in evodiamine-mediated protection against atherosclerosis. Acta Physiol (Oxf) 207, 299– 307. Yao, X. & Garland, C.J. 2005. Recent developments in vascular endothelial cell transient receptor potential channels. Circ Res 97, 853–863.
© 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd, doi: 10.1111/apha.12492
7
Copyright of Acta Physiologica is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
ExActa TRPs revisited Perception of potentially harmful or toxic environmental stimuli is critical for survival of, but not only, highly differentiated organisms. Transient receptor potential (TRP) channels are mostly membrane receptors, located on an extensive array of animal cells from a wide variety of species. More than 45 years ago, Derek Cosens and Aubrey Manning reported to have created a ‘mutant strain of Drosophila melanogaster which, though behaving phototactically positive in a T-maze under low ambient light, is visually impaired and behaves as though blind in a simple optomotor apparatus where normal, wild-type flies will orientate to visual cues’ (Cosens & Manning 1969). Loss of TRP in D. melanogaster results in a transient response (therefore the name) to light, while physiologically, D. melanogaster light response shows sustained photoreceptor cell activity. To date, seven subfamilies have been described, including transient receptor potential canonical (TRPC), transient receptor potential vanilloid (TRPV), transient receptor potential melastatin (TRPM), transient receptor potential polycystin (TRPP), transient receptor potential mucolipin (TRPML), transient receptor potential ankyrin (TRPA) and transient receptor potential ‘No mechanoreceptor potential C’like (TRPN). Apart from TRPN, expressed in invertebrates and fish, most TRP channels may be found throughout the body of numerous species including man (Nilius & Owsianik 2011). Structurally, the subfamilies resemble one another, with mostly six membrane-spanning helices and intracellularly located Cand N-termini. Their function is often sensory in nature. In addition to their role in vision described above, TRP channels are activated in response to stimuli such as high or low temperature or mechanical stimulation. Involvement of TRP channels in taste reception is to some degree debatable. This assumption may be based on the role of polymodal nociceptors in generating the ‘false’ perception of heat or cold by agents such as menthol, capsaicin or allyl isothiocyanate (Wasabi). Why is it that in the English language, which, due to its development on the borders of a historical interface of cultures, having developed into the leading language of international exchange and lingua franca (McCrum et al. 2003), with all its Germanic and Latinate synonyms and nuances, one commonly uses the same word for the sensation brought about by biting on a chilli pepper or by sipping from an overheated drink? ‘Hot’ 6
brings about an interesting ambiguity of taste and temperature sensations, which is not necessarily reflected to a similar degree in other Indogermanic word pools. ‘Pungent’, which reflects the ‘hot taste’ (think Wasabi) sensation transmitted to the CNS by polymodal somatosensory fibres, is much more rarely used. Menthol confuses the body even more than Wasabi does, by simultaneously activating hot and cold fibres, an effect cleverly used when marketing, for example the ‘Icy Hot’ products based on a developmental ‘accident in human physiology’ (Green 1999). Pungency is not a taste in the true sense of the word as its perception is not limited to the taste buds (Ever wiped your eyes after slicing a chilli pepper, anyone?) but, however, an integral part of Eastern cuisine. How do the TRPs do it then? Most are non-selective cation (Na/Ca/Mg) channels, few are selective, for example Ca or hydrated Mg ions. TRPs function mostly as triggers of intracellular Ca release. Channel activation depolarizes the membrane, activating voltage-gated channels (Nilius & Owsianik 2011). TRPs – their location on so many different cell types indicates it – are capable of doing much more, and new functions are regularly described. TRPs are required for endosome and lysosome function and critically involved in cell volume control and, thus, for example control of vascular tone and permeability, mechanosensing, secretion, angiogenesis and endothelial cell (EC) activation, proliferation, apoptosis and death (Yao & Garland 2005). Recently, TRPV1 has been described to be involved in simvastatin-mediated eNOS activation (Su et al. 2014) and phosphorylation (Ching et al. 2013), affecting angiogenesis (Usui et al. 2014, Mittal et al. 2015). TRPVs are involved in pathological states of the circulatory system (Yao & Garland 2005, Wei et al. 2013), neurodegenerative disorders, pain syndromes, skeletal dysplasia and pathologies of the urinary system (Nilius & Owsianik 2011). TRPV1 and 4 are involved in kidney failure, their activation affecting the outcome of ischaemic acute kidney injury (Kassmann et al. 2013), no. 1 cause of hospital-acquired mortality (Kusch et al. 2013, Persson 2013, Pohlmann et al. 2013). Most interestingly, they do so via TRPV1 channels in dorsal root ganglion neurones that innervate the kidney. Urinary bladder regulation is another focus of physiological research (de Groat & Wickens 2013, McCloskey 2013), with some recent interesting publications focusing on generation of bladder-related
© 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd, doi: 10.1111/apha.12492
Acta Physiol 2015, 214, 6–7
autonomous (Ochodnicky et al. 2013) and sensory signals (Birder & Wyndaele 2013) and, specifically, the role of TRP channels in bladder function (Avelino et al. 2013, Burnstock 2013) and idiopathic overactive bladder syndromes (Birder et al. 2013). In 2012, Acta Physiologica devoted a special issue to the results of the International Symposium on G protein-coupled receptors, TRP ion channels and lipid signalling. Let’s look forward to more exciting results on the TRP ion channel family to come.
Conflict of interest None.
P. B. Persson Institute of Vegetative Physiology, Charite-Universitaetsmedizin Berlin, Berlin, Germany E-mail: [email protected]
References Avelino, A., Charrua, A., Frias, B., Cruz, C., Boudes, M., de Ridder, D. & Cruz, F. 2013. Transient receptor potential channels in bladder function. Acta Physiol (Oxf) 207, 110–122. Birder, L. & Wyndaele, J.J. 2013. From urothelial signalling to experiencing a sensation related to the urinary bladder. Acta Physiol (Oxf) 207, 34–39. Birder, L.A., Wolf-Johnston, A.S., Sun, Y. & Chai, T.C. 2013. Alteration in TRPV1 and Muscarinic (M3) receptor expression and function in idiopathic overactive bladder urothelial cells. Acta Physiol (Oxf) 207, 123–129. Burnstock, G. 2013. Purinergic signalling in the lower urinary tract. Acta Physiol (Oxf) 207, 40–52. Ching, L.C., Zhao, J.F., Su, K.H., Shyue, S.K., Hsu, C.P., Lu, T.M., Lin, S.J. & Lee, T.S. 2013. Activation of transient receptor potential vanilloid 1 decreases endothelial nitric oxide synthase phosphorylation at Thr497 by protein phosphatase 2B-dependent dephosphorylation of protein kinase C. Acta Physiol (Oxf) 209, 124–135. Cosens, D.J. & Manning, A. 1969. Abnormal electroretinogram from a Drosophila mutant. Nature 1969, 285–287. Green, B. 1999. Why is it that eating spicy, “hot” food causes the same physical reactions as does physical heat? Scientific American [online] Available at: http://www.scientificamerican.com/article/why-is-it-that-eating-spi/ (accessed March 13, 2015). de Groat, W.C. & Wickens, C. 2013. Organization of the neural switching circuitry underlying reflex micturition. Acta Physiol (Oxf) 207, 66–84.
P B Persson
· ExActa
Kassmann, M., Harteneck, C., Zhu, Z., N€ urnberg, B., Tepel, M. & Gollasch, M. 2013. Transient receptor potential vanilloid 1 (TRPV1), TRPV4, and the kidney. Acta Physiol (Oxf) 207, 546–564. Kusch, A., Hoff, U., Bubalo, G., Zhu, Y., Fechner, M., Schmidt-Ullrich, R., Marko, L., M€ uller, D.N., SchmidtOtt, K.M., G€ urgen, D., Blum, M., Schunck, W.H. & Dragun, D. 2013. Novel signalling mechanisms and targets in renal ischaemia and reperfusion injury. Acta Physiol (Oxf) 2013, 25–40. McCloskey, K.D. 2013. Bladder interstitial cells: an updated review of current knowledge. Acta Physiol (Oxf) 207, 7– 15. McCrum, R., MacNeil, R. & Cran, W. 2003. The Story of English, 3rd revised edn. Penguin Books, London. ISBN 978-0-14-200231-5. Mittal, M., Urao, N., Hecquet, C.M., Zhang, M., Sudhahar, V., Gao, X.P., Komarova, Y., Ushio-Fukai, M. & Malik, A.B. 2015. Novel role of reactive oxygen speciesactivated trp melastatin channel-2 in mediating angiogenesis and postischemic neovascularization. Arterioscler Thromb Vasc Biol ATVBAHA.114.304802. [Epub ahead of print]. Nilius, B. & Owsianik, G. 2011. The transient receptor potential family of ion channels. Genome Biol 12, 218. Ochodnicky, P., Uvelius, B., Andersson, K.E. & Michel, M.C. 2013. Autonomic nervous control of the urinary bladder. Acta Physiol (Oxf) 207, 16–33. Persson, P.B. 2013. Mechanisms of acute kidney injury. Acta Physiol (Oxf) 207, 430–431. Pohlmann, A., Cantow, K., Hentschel, J., Arakelyan, K., Ladwig, M., Flemming, B., Hoff, U., Persson, P.B., Seeliger, E. & Niendorf, T. 2013. Linking non-invasive parametric MRI with invasive physiological measurements (MRPHYSIOL): towards a hybrid and integrated approach for investigation of acute kidney injury in rats. Acta Physiol (Oxf) 207, 673–689. Su, K.H., Lin, S.J., Wei, J., Lee, K.I., Zhao, J.F., Shyue, S.K. & Lee, T.S. 2014. The essential role of transient receptor potential vanilloid 1 in simvastatin-induced activation of endothelial nitric oxide synthase and angiogenesis. Acta Physiol (Oxf) 212, 191–204. Usui, T., Naruo, A., Okada, M., Hayabe, Y. & Yamawaki, H. 2014. Brain-derived neurotrophic factor promotes angiogenic tube formation through generation of oxidative stress in human vascular endothelial cells. Acta Physiol (Oxf) 211, 385–394. Wei, J., Ching, L.C., Zhao, J.F., Shyue, S.K., Lee, H.F., Kou, Y.R. & Lee, T.S. 2013. Essential role of transient receptor potential vanilloid type 1 in evodiamine-mediated protection against atherosclerosis. Acta Physiol (Oxf) 207, 299– 307. Yao, X. & Garland, C.J. 2005. Recent developments in vascular endothelial cell transient receptor potential channels. Circ Res 97, 853–863.
© 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd, doi: 10.1111/apha.12492
7
Copyright of Acta Physiologica is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
