scholarly journals Emerging Roles for Ion Channels in Ovarian Cancer: Pathomechanisms and Pharmacological Treatment

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 668
Author(s):  
Concetta Altamura ◽  
Maria Raffaella Greco ◽  
Maria Rosaria Carratù ◽  
Rosa Angela Cardone ◽  
Jean-François Desaphy
Keyword(s):  
Ovarian Cancer ◽  
Ion Channels ◽  
Transient Receptor Potential ◽  
Critical Role ◽  
Gynecologic Cancer ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Platinum Resistance

Ovarian cancer (OC) is the deadliest gynecologic cancer, due to late diagnosis, development of platinum resistance, and inadequate alternative therapy. It has been demonstrated that membrane ion channels play important roles in cancer processes, including cell proliferation, apoptosis, motility, and invasion. Here, we review the contribution of ion channels in the development and progression of OC, evaluating their potential in clinical management. Increased expression of voltage-gated and epithelial sodium channels has been detected in OC cells and tissues and shown to be involved in cancer proliferation and invasion. Potassium and calcium channels have been found to play a critical role in the control of cell cycle and in the resistance to apoptosis, promoting tumor growth and recurrence. Overexpression of chloride and transient receptor potential channels was found both in vitro and in vivo, supporting their contribution to OC. Furthermore, ion channels have been shown to influence the sensitivity of OC cells to neoplastic drugs, suggesting a critical role in chemotherapy resistance. The study of ion channels expression and function in OC can improve our understanding of pathophysiology and pave the way for identifying ion channels as potential targets for tumor diagnosis and treatment.

In vitro and in vivo evidence for the role of lipid rafts in Ca 2+ ‐gating of the Transient Receptor Potential channels in sensory neurons

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Éva Szőke ◽  
Ádám Horváth ◽  
Tünde Bíró-Sütő ◽  
Éva Sághy ◽  
Maja Payrits ◽  
...  
Keyword(s):  
Lipid Rafts ◽  
Sensory Neurons ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Potential Channels ◽  
Transient Receptor

Heterologously expressed fungal transient receptor potential channels retain mechanosensitivity in vitro and osmotic response in vivo

2005 ◽  
Vol 34 (5) ◽  
pp. 413-422 ◽  
Author(s):  
Xin-liang Zhou ◽  
Steven H. Loukin ◽  
Roberto Coria ◽  
Ching Kung ◽  
Yoshiro Saimi
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Osmotic Response ◽  
Potential Channels ◽  
Transient Receptor

scholarly journals The transient receptor potential, TRP4, cation channel is a novel member of the family of calmodulin binding proteins

2001 ◽  
Vol 355 (3) ◽  
pp. 663-670 ◽  
Author(s):  
Claudia TROST ◽  
Christiane BERGS ◽  
Nina HIMMERKUS ◽  
Veit FLOCKERZI
Keyword(s):  
Amino Acid ◽  
Ion Channels ◽  
Transient Receptor Potential ◽  
Direct Interaction ◽  
Receptor Potential ◽  
Amino Acid Residues ◽  
Glutathione S Transferase ◽  
Calmodulin Binding ◽  
Transient Receptor

The mammalian gene products, transient receptor potential (trp)1 to trp7, are related to the Drosophila TRP and TRP-like ion channels, and are candidate proteins underlying agonist-activated Ca2+-permeable ion channels. Recently, the TRP4 protein has been shown to be part of native store-operated Ca2+-permeable channels. These channels, most likely, are composed of other proteins in addition to TRP4. In the present paper we report the direct interaction of TRP4 and calmodulin (CaM) by: (1) retention of in vitro translated TRP4 and of TRP4 protein solubilized from bovine adrenal cortex by CaM–Sepharose in the presence of Ca2+, and (2) TRP4–glutathione S-transferase pull-down experiments. Two domains of TRP4, amino acid residues 688–759 and 786–848, were identified as being able to interact with CaM. The binding of CaM to both domains occurred only in the presence of Ca2+ concentrations above 10µM, with half maximal binding occurring at 16.6µM (domain 1) and 27.9µM Ca2+ (domain 2). Synthetic peptides, encompassing the two putative CaM binding sites within these domains and covering amino acid residues 694–728 and 829–853, interacted directly with dansyl–CaM with apparent Kd values of 94–189nM. These results indicate that TRP4/Ca2+-CaM are parts of a signalling complex involved in agonist-induced Ca2+ entry.

scholarly journals Novel role of transient receptor potential vanilloid 2 in the regulation of cardiac performance

2014 ◽  
Vol 306 (4) ◽  
pp. H574-H584 ◽  
Author(s):  
Jack Rubinstein ◽  
Valerie M. Lasko ◽  
Sheryl E. Koch ◽  
Vivek P. Singh ◽  
Vinicius Carreira ◽  
...  
Keyword(s):  
Vascular Function ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Wild Type ◽  
Transient Receptor ◽  
Systolic And Diastolic Function ◽  
Myocyte Contractility

Transient receptor potential cation channels have been implicated in the regulation of cardiovascular function, but only recently has our laboratory described the vanilloid-2 subtype (TRPV2) in the cardiomyocyte, though its exact mechanism of action has not yet been established. This study tests the hypothesis that TRPV2 plays an important role in regulating myocyte contractility under physiological conditions. Therefore, we measured cardiac and vascular function in wild-type and TRPV2−/− mice in vitro and in vivo and found that TRPV2 deletion resulted in a decrease in basal systolic and diastolic function without affecting loading conditions or vascular tone. TRPV2 stimulation with probenecid, a relatively selective TRPV2 agonist, caused an increase in both inotropy and lusitropy in wild-type mice that was blunted in TRPV2−/− mice. We examined the mechanism of TRPV2 inotropy/lusitropy in isolated myocytes and found that it modulates Ca2+ transients and sarcoplasmic reticulum Ca2+ loading. We show that the activity of this channel is necessary for normal cardiac function and that there is increased contractility in response to agonism of TRPV2 with probenecid.

scholarly journals TRPM4 Channels Couple Purinergic Receptor Mechanoactivation and Myogenic Tone Development in Cerebral Parenchymal Arterioles

2014 ◽  
Vol 34 (10) ◽  
pp. 1706-1714 ◽  
Author(s):  
Yao Li ◽  
Rachael L Baylie ◽  
Matthew J Tavares ◽  
Joseph E Brayden
Keyword(s):  
Transient Receptor Potential ◽  
Purinergic Receptor ◽  
Critical Role ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Receptor Activation ◽  
Myogenic Tone ◽  
Pial Arteries ◽  
Myogenic Regulation

Cerebral parenchymal arterioles (PAs) have a critical role in assuring appropriate blood flow and perfusion pressure within the brain. They are unique in contrast to upstream pial arteries, as defined by their critical roles in neurovascular coupling, distinct sensitivities to chemical stimulants, and enhanced myogenic tone development. The objective of the present study was to reveal some of the unique mechanisms of myogenic tone regulation in the cerebral microcirculation. Here, we report that in vivo suppression of TRPM4 (transient receptor potential) channel expression, or inhibition of TRPM4 channels with 9-phenanthrol substantially reduced myogenic tone of isolated PAs, supporting a key role of TRPM4 channels in PA myogenic tone development. Further, downregulation of TRPM4 channels inhibited vasoconstriction induced by the specific P2Y4 and P2Y6 receptor ligands (UTP γS and UDP) by 37% and 42%, respectively. In addition, 9-phenanthrol substantially attenuated purinergic ligand-induced membrane depolarization and constriction of PAs, and inhibited ligand-evoked TRPM4 channel activation in isolated PA myocytes. In concert with our previous work showing the essential contributions of P2Y4 and P2Y6 receptors to myogenic regulation of PAs, the current results point to TRPM4 channels as an important link between mechanosensitive P2Y receptor activation and myogenic constriction of cerebral PAs.

Mechanisms and Physiological Implications of Cooperative Gating of Ion Channels Clusters

2021 ◽  
Author(s):  
Rose Ellen Dixon ◽  
Manuel F. Navedo ◽  
Marc D Binder ◽  
L. Fernando Santana
Keyword(s):  
Ion Channels ◽  
Action Potential ◽  
Transient Receptor Potential ◽  
Imaging Techniques ◽  
Ryanodine Receptors ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Cardiac Cells ◽  
Fine Tuning ◽  
Voltage Gated

Ion channels play a central role in the regulation of nearly every cellular process. Dating back to the classic 1952 Hodgkin-Huxley model of the generation of the action potential, ion channels have always been thought of as independent agents. A myriad of recent experimental findings exploiting advances in electrophysiology, structural biology, and imaging techniques, however, have posed a serious challenge to this long-held axiom as several classes of ion channels appear to open and close in a coordinated, cooperative manner. Ion channel cooperativity ranges from variable-sized oligomeric cooperative gating in voltage-gated, dihydropyridine-sensitive Cav1.2 and Cav1.3 channels to obligatory dimeric assembly and gating of voltage-gated Nav1.5 channels. Potassium channels, transient receptor potential channels, hyperpolarization cyclic nucleotide-activated channels, ryanodine receptors (RyRs), and inositol trisphosphate receptors (IP3Rs) have also been shown to gate cooperatively. The implications of cooperative gating of these ion channels range from fine tuning excitation-contraction coupling in muscle cells to regulating cardiac function and vascular tone, to modulation of action potential and conduction velocity in neurons and cardiac cells, and to control of pace-making activity in the heart. In this review, we discuss the mechanisms leading to cooperative gating of ion channels, their physiological consequences and how alterations in cooperative gating of ion channels may induce a range of clinically significant pathologies.

scholarly journals TRPC1 participates in the HSV-1 infection process by facilitating viral entry

2020 ◽  
Vol 6 (12) ◽  
pp. eaaz3367 ◽  
Author(s):  
DongXu He ◽  
AiQin Mao ◽  
YouRan Li ◽  
SiuCheung Tam ◽  
YongTang Zheng ◽  
...  
Keyword(s):  
Viral Entry ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Critical Role ◽  
Receptor Potential ◽  
Infection Process ◽  
Ocular Abnormality ◽  
Simplex Virus ◽  
Hsv 1

Mammalian transient receptor potential (TRP) channels are major components of Ca2+ signaling pathways and control a diversity of physiological functions. Here, we report a specific role for TRPC1 in the entry of herpes simplex virus type 1 (HSV-1) into cells. HSV-1–induced Ca2+ release and entry were dependent on Orai1, STIM1, and TRPC1. Inhibition of Ca2+ entry or knockdown of these proteins attenuated viral entry and infection. HSV-1 glycoprotein D interacted with the third ectodomain of TRPC1, and this interaction facilitated viral entry. Knockout of TRPC1 attenuated HSV-1–induced ocular abnormality and morbidity in vivo in TRPC1−/− mice. There was a strong correlation between HSV-1 infection and plasma membrane localization of TRPC1 in epithelial cells within oral lesions in buccal biopsies from HSV-1–infected patients. Together, our findings demonstrate a critical role for TRPC1 in HSV-1 infection and suggest the channel as a potential target for anti-HSV therapy.

scholarly journals Calcium-permeable ion channels in the kidney

2016 ◽  
Vol 310 (11) ◽  
pp. F1157-F1167 ◽  
Author(s):  
Yiming Zhou ◽  
Anna Greka
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Transient Receptor Potential ◽  
Kidney Development ◽  
Kidney Diseases ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Cellular Functions ◽  
Potential Channels ◽  
Transient Receptor

Calcium ions (Ca2+) are crucial for a variety of cellular functions. The extracellular and intracellular Ca2+ concentrations are thus tightly regulated to maintain Ca2+ homeostasis. The kidney, one of the major organs of the excretory system, regulates Ca2+ homeostasis by filtration and reabsorption. Approximately 60% of the Ca2+ in plasma is filtered, and 99% of that is reabsorbed by the kidney tubules. Ca2+ is also a critical signaling molecule in kidney development, in all kidney cellular functions, and in the emergence of kidney diseases. Recently, studies using genetic and molecular biological approaches have identified several Ca2+-permeable ion channel families as important regulators of Ca2+ homeostasis in kidney. These ion channel families include transient receptor potential channels (TRP), voltage-gated calcium channels, and others. In this review, we provide a brief and systematic summary of the expression, function, and pathological contribution for each of these Ca2+-permeable ion channels. Moreover, we discuss their potential as future therapeutic targets.

Involvement of the vanilloid receptor 1 in the mechanisms of analgesic effect of amizonum

2014 ◽  
Vol 31 (1) ◽  
pp. 41-49
Author(s):  
Oleh Yadlovskyi ◽  
Tatiana Bukhtiarova ◽  
Lyudmila Bobkova ◽  
Irina Tatianshenko ◽  
Igor Monchak ◽  
...  
Keyword(s):  
Portal Vein ◽  
Active Site ◽  
Analgesic Effect ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Theoretical Background ◽  
Tail Flick ◽  
Intermolecular Complex

SUMMARY The study of features of pharmacodynamics of a new analgesic is an important and urgent task of modern pharmacology. These data allow us to clarify the nosology for application of an analgesic and to create a theoretical background to optimize its use. An effect mediated by the transient receptor potential cation channel, subfamily V, member 1 (TRPV1) activation can also be an effective mechanism of the analgesic action. We evaluated the possibility of TRPV1 participation in implementation of the analgesic effect with the antiviral action of amizonum during the experiment. It is known that amino acids Tyr511 and Ser512 are the main components of the active site of TRPV1. In this connection, dipeptide Tyr-Ser has been completely synthesized as a model of the active site of TRPV1. In the experiment model this was shown, using the spectrophotometric method, with the formation of the “capsaicin - Tyr- Ser” intermolecular complex at the level of the stability constant Kkor=0.998 and Kr=0.3•10-4 L/mol and the “amizonum - Tyr-Ser” weak intermolecular complex Kr=0.05•104 L/mol; Kkor= 0.995, respectively. The data verification was carried out in experiments in vitro (isolated ratportal vein) and in vivo (Tail-flick model), with the TRPV1 agonist. It was shown that the amplitude of smooth muscle (SM) contraction of the portal vein at a capsaicin concentration 0.1 μmol/L, 0.5 μmol/L capsazepine, and 1.0 μmol/L amizonum was +30.3±5.3%, -3.2± 2.7% and +7.1±3.2% from initial level, respectivelly. In a combined application of amizonum with capsaicin or capsazepine, the amplitude of contraction of the SM portal vein was 20.1± 1.3% and -3.0±1.4%, respectively. This indicates the absence of action of amizonum under combined use of capsaicinoids. The Tail-flick model showed atypical potentiation of the amizonum antinociception with the use of capsaicin. The obtained data suggest the low probability of the participation of TRPV1 in the implementation of the antinociceptive action of amizonum.

Abstract 1287: TRPV4-Deficient Mice Exhibit Impaired Endothelium-Dependent Relaxation Induced by Acetylcholine in Vitro and in Vivo

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
David Zhang ◽  
Suelhem Mendoza ◽  
Aaron Bubolz ◽  
Makoto Suzuki ◽  
David Gutterman
Keyword(s):  
Blood Pressure ◽  
Endothelial Cells ◽  
Carotid Arteries ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Mice Model ◽  
Synthase Inhibitor

Agonist-induced Ca 2+ entry in endothelial cells is important for the synthesis and release of vasoactive factors, although mechanisms of Ca 2+ entry remain largely unknown. Emerging evidence suggests that the transient receptor potential vanilloid 4 (TRPV4) channel, a Ca 2+ -permeant TRP channel, is expressed in endothelial cells and may be involved in the regulation of vascular tone. Here we investigated the potential role of TRPV4 channels in acetylcholine-induced vasodilation in vitro and in vivo using the TRPV4 knockout (TRPV4 −/− ) mice model. Carotid arteries were isolated and preconstricted with the thromboxane A2 mimetic U46619. Concentration-dependent relaxations to acetylcholine (10 −9 –10 −5 M) were markedly reduced in carotids of TRPV4 −/− vs. wild-type (WT) mice (maximal relaxations of 31±12% vs 53±4%, respectively; n=4 mice). There was no significant change in the ED50 for Ach. In both WT and TRPV4 −/− , acetylcholine-induced relaxations were blocked and converted to constrictions by the NO synthase inhibitor L-NAME (maximal relaxations of −25±6% and −24±7%, respectively). There was no difference in papaverine-induced relaxations between WT and TRPV4 −/− mice (maximal relaxations of 93±3% vs. 90±3%, respectively). U46619 caused similar contractions in carotid arteries from those mice. We also compared in vivo vasodilator effects of acetylcholine by measuring changes in blood pressure in those animals. Intravenous administration of acetylcholine (15 ng/gm bolus) decreased blood pressure by 32±6 mmHg in WT mice (from 90±15 to 57±10 mmHg; n=6), whereas blood pressure was reduced by only 10 mmHg in TRPV4 −/− mice (from 67±6 to 56±4 mmHg; n=12). Acetylcholine caused similar reductions in heart rate in WT and TRPV4 −/− mice, with mean changes of 365±57 and 292±40 beats/min, respectively. We conclude that the endothelium-dependent vasodilator response to acetylcholine is reduced both in vitro and in vivo in TRPV4 −/− mice, and these findings may provide novel insight into the mechanisms of Ca 2+ entry evoked by chemical agonists in endothelial cells. The paradoxically lower baseline blood pressure in TRPV4 −/− mice requires further investigation.

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