Pleiotropic function of TRPV4 ion channels in the central nervous system

Kanju, Patrick; Liedtke, Wolfgang

doi:10.1113/ep085790

Cited by 38 publications

(34 citation statements)

References 45 publications

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“…a search for ''TRPV4 pain'' generated 185 references out of a total of 1085 references for ''TRPV4''. Primary sensory neurons with TRPV4 expression include pain-sensing neurons in the DRG [8,255,256] and TG [257,258] [ 94,259], most recently also satellite cells in sensory ganglia [260], in the CNS for pain transmission in astrocytes [261], microglial cells [262], and neurons [263,264,265]. Outside the nervous system, TRPV4 has been found in innervated cells such as prominently in chondrocytes [266], vascular endothelia [267], and innervated epithelia such as skin keratinocytes [129,268], airway epithelial cells [26,269,270], colonic epithelia [271], and odontoblasts [272].…”

Section: Trpv4 Functions As a Pain-trp And An Itch-trpmentioning

confidence: 99%

Regulation of Pain and Itch by TRP Channels

et al. 2017

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Nociception is an important physiological process that detects harmful signals and results in pain perception. In this review, we discuss important experimental evidence involving some TRP ion channels as molecular sensors of chemical, thermal, and mechanical noxious stimuli to evoke the pain and itch sensations. Among them are the TRPA1 channel, members of the vanilloid subfamily (TRPV1, TRPV3, and TRPV4), and finally members of the melastatin group (TRPM2, TRPM3, and TRPM8). Given that pain and itch are pro-survival, evolutionarily-honed protective mechanisms, care has to be exercised when developing inhibitory/modulatory compounds targeting specific pain/itch-TRPs so that physiological protective mechanisms are not disabled to a degree that stimulus-mediated injury can occur. Such events have impeded the development of safe and effective TRPV1-modulating compounds and have diverted substantial resources. A beneficial outcome can be readily accomplished via simple dosing strategies, and also by incorporating medicinal chemistry design features during compound design and synthesis. Beyond clinical use, where compounds that target more than one channel might have a place and possibly have advantageous features, highly specific and high-potency compounds will be helpful in mechanistic discovery at the structure-function level.

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Section: Trpv4 Functions As a Pain-trp And An Itch-trpmentioning

confidence: 99%

Regulation of Pain and Itch by TRP Channels

et al. 2017

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“…We demonstrated that intravascular pressure‐evoked increases in astrocyte Ca 2+ are partly mediated via TRPV4 channel activation (Kim et al, ). TRPV4 are Ca 2+ permeable nonselective cation channels (Plant & Strotmann, ) involved in numerous functions including, systemic tonicity, mechanosensation, pain, inflammation, and vascular tone (Earley et al, ; Hill‐Eubanks, Gonzales, Sonkusare, & Nelson, ; Kanju & Liedtke, ; Plant & Strotmann, ; Ryskamp, Iuso, & Krizaj, ; Vriens, Janssens, Prenen, Nilius, & Wondergem, ). TRPV4 channels expressed in the vasculature serve as molecular detectors and transducers of arteriole myogenic responses (e.g., mechanical stress; Kim et al, ).…”

Section: Introductionmentioning

confidence: 99%

Augmented astrocyte microdomain Ca²⁺ dynamics and parenchymal arteriole tone in angiotensin II‐infused hypertensive mice

Diaz

Kim

Brands

et al. 2018

Glia

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Hypertension is an important contributor to cognitive decline but the underlying mechanisms are unknown. Although much focus has been placed on the effect of hypertension on vascular function, less is understood of its effects on nonvascular cells. Because astrocytes and parenchymal arterioles (PA) form a functional unit (neurovascular unit), we tested the hypothesis that hypertension‐induced changes in PA tone concomitantly increases astrocyte Ca2+. We used cortical brain slices from 8‐week‐old mice to measure myogenic responses from pressurized and perfused PA. Chronic hypertension was induced in mice by 28‐day angiotensin II (Ang II) infusion; PA resting tone and myogenic responses increased significantly. In addition, chronic hypertension significantly increased spontaneous Ca2+ events within astrocyte microdomains (MD). Similarly, a significant increase in astrocyte Ca2+ was observed during PA myogenic responses supporting enhanced vessel‐to‐astrocyte signaling. The transient potential receptor vanilloid 4 (TRPV4) channel, expressed in astrocyte processes in contact with blood vessels, namely endfeet, respond to hemodynamic stimuli such as increased pressure/flow. Supporting a role for TRPV4 channels in aberrant astrocyte Ca2+ dynamics in hypertension, cortical astrocytes from hypertensive mice showed augmented TRPV4 channel expression, currents and Ca2+ responses to the selective channel agonist GSK1016790A. In addition, pharmacological TRPV4 channel blockade or genetic deletion abrogated enhanced hypertension‐induced increases in PA tone. Together, these data suggest chronic hypertension increases PA tone and Ca2+ events within astrocytes MD. We conclude that aberrant Ca2+ events in astrocyte constitute an early event toward the progression of cognitive decline.

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“…Expression of TRPV4 in mammals is wide-spread. It is expressed in the central and peripheral nervous system 15 , noticeably in tissues involved in volume regulation and osmosensing such as the circumventricular organs, the vascular endothelium and the kidney 12 , 16 , 17 . In an earlier study expression of TRPV4 in the kidney has been reported to be restricted to the distal part of the renal nephron system, which is constitutively or conditionally water–impermeable 18 , thereby supporting its osmoregulatory role 17 .…”

Section: Introductionmentioning

confidence: 99%

Transient Receptor Potential Vanilloid 4 Channel Deficiency Aggravates Tubular Damage after Acute Renal Ischaemia Reperfusion

Mannaa

Markó

Balogh

et al. 2018

Sci Rep

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Transient receptor potential vanilloid 4 (TRPV4) cation channels are functional in all renal vascular segments and mediate endothelium-dependent vasorelaxation. Moreover, they are expressed in distinct parts of the tubular system and activated by cell swelling. Ischaemia/reperfusion injury (IRI) is characterized by tubular injury and endothelial dysfunction. Therefore, we hypothesised a putative organ protective role of TRPV4 in acute renal IRI. IRI was induced in TRPV4 deficient (Trpv4 KO) and wild–type (WT) control mice by clipping the left renal pedicle after right–sided nephrectomy. Serum creatinine level was higher in Trpv4 KO mice 6 and 24 hours after ischaemia compared to WT mice. Detailed histological analysis revealed that IRI caused aggravated renal tubular damage in Trpv4 KO mice, especially in the renal cortex. Immunohistological and functional assessment confirmed TRPV4 expression in proximal tubular cells. Furthermore, the tubular damage could be attributed to enhanced necrosis rather than apoptosis. Surprisingly, the percentage of infiltrating granulocytes and macrophages were comparable in IRI–damaged kidneys of Trpv4 KO and WT mice. The present results suggest a renoprotective role of TRPV4 during acute renal IRI. Further studies using cell–specific TRPV4 deficient mice are needed to clarify cellular mechanisms of TRPV4 in IRI.

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Pleiotropic function of TRPV4 ion channels in the central nervous system

Cited by 38 publications

References 45 publications

Regulation of Pain and Itch by TRP Channels

Regulation of Pain and Itch by TRP Channels

Augmented astrocyte microdomain Ca²⁺ dynamics and parenchymal arteriole tone in angiotensin II‐infused hypertensive mice

Transient Receptor Potential Vanilloid 4 Channel Deficiency Aggravates Tubular Damage after Acute Renal Ischaemia Reperfusion

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Pleiotropic function of TRPV4 ion channels in the central nervous system

Cited by 38 publications

References 45 publications

Regulation of Pain and Itch by TRP Channels

Regulation of Pain and Itch by TRP Channels

Augmented astrocyte microdomain Ca2+ dynamics and parenchymal arteriole tone in angiotensin II‐infused hypertensive mice

Transient Receptor Potential Vanilloid 4 Channel Deficiency Aggravates Tubular Damage after Acute Renal Ischaemia Reperfusion

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Augmented astrocyte microdomain Ca²⁺ dynamics and parenchymal arteriole tone in angiotensin II‐infused hypertensive mice