Local control of TRPV4 channels by AKAP150-targeted PKC in arterial smooth muscle

Mercado, Jose; Baylie, Rachael; Navedo, Manuel F.; Yuan, Can; Scott, John D.; Nelson, Mark T.; Brayden, Joseph E.; Santana, Luis Fernando

doi:10.1085/jgp.201311050

Cited by 93 publications

(109 citation statements)

References 45 publications

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“…Our results also reveal a potent inhibitory role of NO on TRPV4 channel function, defining it as a novel physiological regulator (limiter) of TRPV4 channels (Figure 8). TRPV4 channels are Ca 2+ ‐selective cation channels with a large single channel conductance; the amount of Ca 2+ entering through 1 TRPV4 channel is ≈100 times higher than an L‐type Ca 2+ channel 72. A slight overactivation of TRPV4 channels could lead to Ca 2+ overload.…”

Section: Discussionmentioning

confidence: 99%

Nitric Oxide–Dependent Feedback Loop Regulates Transient Receptor Potential Vanilloid 4 (TRPV4) Channel Cooperativity and Endothelial Function in Small Pulmonary Arteries

Marziano

Hong

Cope

et al. 2017

JAHA

132

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BackgroundRecent studies demonstrate that spatially restricted, local Ca2+ signals are key regulators of endothelium‐dependent vasodilation in systemic circulation. There are drastic functional differences between pulmonary arteries (PAs) and systemic arteries, but the local Ca2+ signals that control endothelium‐dependent vasodilation of PAs are not known. Localized, unitary Ca2+ influx events through transient receptor potential vanilloid 4 (TRPV4) channels, termed TRPV4 sparklets, regulate endothelium‐dependent vasodilation in resistance‐sized mesenteric arteries via activation of Ca2+‐dependent K+ channels. The objective of this study was to determine the unique functional roles, signaling targets, and endogenous regulators of TRPV4 sparklets in resistance‐sized PAs.Methods and ResultsUsing confocal imaging, custom image analysis, and pressure myography in fourth‐order PAs in conjunction with knockout mouse models, we report a novel Ca2+ signaling mechanism that regulates endothelium‐dependent vasodilation in resistance‐sized PAs. TRPV4 sparklets exhibit distinct spatial localization in PAs when compared with mesenteric arteries, and preferentially activate endothelial nitric oxide synthase (eNOS). Nitric oxide released by TRPV4‐endothelial nitric oxide synthase signaling not only promotes vasodilation, but also initiates a guanylyl cyclase‐protein kinase G‐dependent negative feedback loop that inhibits cooperative openings of TRPV4 channels, thus limiting sparklet activity. Moreover, we discovered that adenosine triphosphate dilates PAs through a P2 purinergic receptor‐dependent activation of TRPV4 sparklets.ConclusionsOur results reveal a spatially distinct TRPV4‐endothelial nitric oxide synthase signaling mechanism and its novel endogenous regulators in resistance‐sized PAs.

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Section: Discussionmentioning

confidence: 99%

Nitric Oxide–Dependent Feedback Loop Regulates Transient Receptor Potential Vanilloid 4 (TRPV4) Channel Cooperativity and Endothelial Function in Small Pulmonary Arteries

Marziano

Hong

Cope

et al. 2017

JAHA

132

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“…GPCRs have been reported to regulate TRP channels by modulating protein kinase activity (29,49,(51)(52)(53). To determine whether PKC mediates P2Y 1 sensitization or activation of TRPV4, we preincubated HEK-TRPV4 cells with Go6983 (1 M; a broad spectrum PKC inhibitor (32)), Go6976 (1 M; a selective inhibitor of PKC␣ and PKC␤1 isoforms (31)), or vehicle (control).…”

Section: Volume 290 • Number 48 • November 27 2015mentioning

confidence: 99%

P2Y1 Receptor Activation of the TRPV4 Ion Channel Enhances Purinergic Signaling in Satellite Glial Cells

Rajasekhar

Poole

Liedtke

et al. 2015

Journal of Biological Chemistry

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Background:The function of TRP channels in satellite glial cells is unknown. Results: The proinflammatory, mechanosensitive TRPV4 channel is expressed by satellite glial cells. P2Y 1 receptors cause protein kinase C-dependent activation of TRPV4. Conclusion: TRPV4 enhances purinergic signaling in non-neuronal cells of sensory ganglia. Significance: TRPV4-mediated signaling in satellite glial cells may contribute to inflammatory pain.

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“…These observations were supported by demonstrating reduced calcium influx to 4-␣-PDD in HEK-293 cells following ANG II stimulation. Another recent study using arterial myocytes reports that ANG II increases TRPV4 activity through a G protein mechanism that is dependent on PKC and anchoring protein AKAP150 (44). An important feature of these results is that the modulation of TRPV4 in this cell type occurred in spatially restricted microdomains that may have facilitated the interaction of these proteins.…”

Section: Discussionmentioning

confidence: 81%

“…For example, the presence of G protein-coupled receptor kinases in association with angiotensin receptors could prevent G proteinmediated signaling and facilitate ␤-arrestin binding (70). In contrast, a differently organized membrane domain lacking these kinases would allow for G protein-mediated effects that could be directed by the availability of other substrates such as AKAP150 (44). This type of membrane organization could be dynamically regulated (61).…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II induces membrane trafficking of natively expressed transient receptor potential vanilloid type 4 channels in hypothalamic 4B cells

Saxena

Bachelor

Park

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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We previously reported that in the rodent, a model of dilutional hyponatremia associated with hepatic cirrhosis, TRPV4 expression is increased in lipid rafts from the hypothalamus and that this effect may be angiotensin dependent. In this study, we utilized the immortalized neuroendocrine rat hypothalamic 4B cell line to more directly test the effects of angiotensin II (ANG II) on TRPV4 expression and function. Our results demonstrate the expression of corticotropin-releasing factor (CRF) transcripts, for sex-determining region Y (SRY) (male genotype), arginine vasopressin (AVP), TRPV4, and ANG II type 1a and 1b receptor in 4B cells. After a 1-h incubation in ANG II (100 nM), 4B cells showed increased TRPV4 abundance in the plasma membrane fraction, and this effect was prevented by the ANG II type 1 receptor antagonist losartan (1 M) and by a Src kinase inhibitor PP2 (10 M). Ratiometric calcium imaging experiments demonstrated that ANG II incubation potentiated TRPV4 agonist (GSK 1016790A, 20 nM)-induced calcium influx (control 18.4 Ϯ 2.8% n ϭ 5 and ANG II 80.5 Ϯ 2.4% n ϭ 5). This ANG II-induced increase in calcium influx was also blocked by 1 M losartan and 10 M PP2 (losartan 26.4 Ϯ 3.8% n ϭ 5 and PP2 19.7 Ϯ 3.9% n ϭ 5). Our data suggests that ANG II can increase TRPV4 channel membrane expression in 4B cells through its action on AT1R involving a Src kinase pathway.angiotensin; TRPV4; hypothalamus; 4B; SRC kinase; SRY TRANSIENT RECEPTOR POTENTIAL (TRP) channel superfamily plays a central role in sensory physiology (47, 54). The TRP subfamily vanilloid member 4 (TRPV4) is a nonselective cation channel that is calcium permeable and shows polymodal activation by diverse stimuli including, but not limited to, moderate heat, cell swelling, and endogenous ligands (51,55,69). Functionally, it is strongly implicated in a number of physiological systems that include endothelial function and vascular tone (21, 64), renal function (56), central osmosensation (41, 46), and regulating hydromineral homeostasis (51, 55, 69). Mutations of TRPV4 are linked to a number of motor and sensory neuropathies and skeletal dysplasias (51, 69).TRPV4 is expressed in central nervous system (CNS) regions involved in neuroendocrine function including neurosecretory cells in the supraoptic nucleus (SON) and the paraventricular nuclei of the hypothalamus (PVN) (3, 9). In a rodent model of cirrhosis, we have previously reported increased TRPV4 trafficking to lipid rafts in hypothalamic samples that contained the SON, the PVN, and the organum vasculosum of the lamina terminalis (9). Importantly, we also found that increased TRPV4 trafficking correlated with activation of renin-angiotensin system (RAS) and was reversed after RAS inhibition (9).Angiotensin II (ANG II) is an effector molecule of RAS (25). Circulating ANG II is known to contribute to water and electrolyte homeostasis peripherally and centrally through its actions on blood-brain barrier-deficient circumventricular organs in the forebrain and dorsal hindbrain (31, 43). As part of the ...

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Local control of TRPV4 channels by AKAP150-targeted PKC in arterial smooth muscle

Abstract: Angiotensin signaling promotes interactions between AKAP150, PKC, and TRPV4 channels to form signaling domains that control Ca2+ influx into arterial myocytes.

Cited by 93 publications

References 45 publications

Nitric Oxide–Dependent Feedback Loop Regulates Transient Receptor Potential Vanilloid 4 (TRPV4) Channel Cooperativity and Endothelial Function in Small Pulmonary Arteries

Nitric Oxide–Dependent Feedback Loop Regulates Transient Receptor Potential Vanilloid 4 (TRPV4) Channel Cooperativity and Endothelial Function in Small Pulmonary Arteries

P2Y1 Receptor Activation of the TRPV4 Ion Channel Enhances Purinergic Signaling in Satellite Glial Cells

Angiotensin II induces membrane trafficking of natively expressed transient receptor potential vanilloid type 4 channels in hypothalamic 4B cells

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