Finely-Tuned Calcium Oscillations in Osteoclast Differentiation and Bone Resorption

Calcium (Ca2+) plays an important role in regulating the differentiation and function of osteoclasts. Calcium oscillations (Ca oscillations) are well-known phenomena in receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastogenesis and bone resorption via calcineurin. Many modifiers are involved in the fine-tuning of Ca oscillations in osteoclasts. In addition to macrophage colony-stimulating factors (M-CSF; CSF-1) and RANKL, costimulatory signaling by immunoreceptor tyrosine-based activation motif-harboring adaptors is important for Ca oscillation generation and osteoclast differentiation. DNAX-activating protein of 12 kD is always necessary for osteoclastogenesis. In contrast, Fc receptor gamma (FcRγ) works as a key controller of osteoclastogenesis especially in inflammatory situation. FcRγ has a cofactor in fine-tuning of Ca oscillations. Some calcium channels and transporters are also necessary for Ca oscillations. Transient receptor potential (TRP) channels are well-known environmental sensors, and TRP vanilloid channels play an important role in osteoclastogenesis. Lysosomes, mitochondria, and endoplasmic reticulum (ER) are typical organelles for intracellular Ca2+ storage. Ryanodine receptor, inositol trisphosphate receptor, and sarco/endoplasmic reticulum Ca2+ ATPase on the ER modulate Ca oscillations. Research on Ca oscillations in osteoclasts has still many problems. Surprisingly, there is no objective definition of Ca oscillations. Causality between Ca oscillations and osteoclast differentiation and/or function remains to be examined.

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Pulsed infrared releases Ca2+ from the endoplasmic reticulum of cultured spiral ganglion neurons

Journal of Neurophysiology ◽

10.1152/jn.00740.2017 ◽

2018 ◽

Vol 120 (2) ◽

pp. 509-524 ◽

Cited By ~ 9

Author(s):

John N. Barrett ◽

Samantha Rincon ◽

Jayanti Singh ◽

Cristina Matthewman ◽

Julio Pasos ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Infrared Radiation ◽

Transient Receptor Potential ◽

Trp Channels ◽

Spiral Ganglion ◽

Receptor Potential ◽

Transient Temperature ◽

Spiral Ganglion Neurons ◽

Transient Receptor ◽

Ganglion Neurons

Inner ear spiral ganglion neurons were cultured from day 4 postnatal mice and loaded with a fluorescent Ca2+ indicator (fluo-4, -5F, or -5N). Pulses of infrared radiation (IR; 1,863 nm, 200 µs, 200–250 Hz for 2–5 s, delivered via an optical fiber) produced a rapid, transient temperature increase of 6–12°C (above a baseline of 24–30°C). These IR pulse trains evoked transient increases in both nuclear and cytosolic Ca2+ concentration ([Ca2+]) of 0.20–1.4 µM, with a simultaneous reduction of [Ca2+] in regions containing endoplasmic reticulum (ER). IR-induced increases in cytosolic [Ca2+] continued in medium containing no added Ca2+ (±Ca2+ buffers) and low [Na+], indicating that the [Ca2+] increase was mediated by release from intracellular stores. Consistent with this hypothesis, the IR-induced [Ca2+] response was prolonged and eventually blocked by inhibition of ER Ca2+-ATPase with cyclopiazonic acid, and was also inhibited by a high concentration of ryanodine and by inhibitors of inositol (1,4,5)-trisphosphate (IP3)-mediated Ca2+ release (xestospongin C and 2-aminoethoxydiphenyl borate). The thermal sensitivity of the response suggested involvement of warmth-sensitive transient receptor potential (TRP) channels. The IR-induced [Ca2+] increase was inhibited by TRPV4 inhibitors (HC-067047 and GSK-2193874), and immunostaining of spiral ganglion cultures demonstrated the presence of TRPV4 and TRPM2 that colocalized with ER marker GRP78. These results suggest that the temperature sensitivity of IR-induced [Ca2+] elevations is conferred by TRP channels on ER membranes, which facilitate Ca2+ efflux into the cytosol and thereby contribute to Ca2+-induced Ca2+-release via IP3 and ryanodine receptors. NEW & NOTEWORTHY Infrared radiation-induced photothermal effects release Ca2+ from the endoplasmic reticulum of primary spiral ganglion neurons. This Ca2+ release is mediated by activation of transient receptor potential (TRPV4) channels and involves amplification by Ca2+-induced Ca2+-release. The neurons immunostained for warmth-sensitive channels, TRPV4 and TRPM2, which colocalize with endoplasmic reticulum. Pulsed infrared radiation provides a novel experimental tool for releasing intracellular Ca2+, studying Ca2+ regulatory mechanisms, and influencing neuronal excitability.

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Fine Tuning of Calcium Constitutive Entry by Optogenetically-Controlled Membrane Polarization: Impact on Cell Migration

Cells ◽

10.3390/cells9071684 ◽

2020 ◽

Vol 9 (7) ◽

pp. 1684

Author(s):

Charles-Albert Chapotte-Baldacci ◽

Guénaëlle Lizot ◽

Cyrielle Jajkiewicz ◽

Manuella Lévêque ◽

Aubin Penna ◽

...

Keyword(s):

Cell Migration ◽

Transient Receptor Potential ◽

Trp Channels ◽

Receptor Potential ◽

Calcium Entry ◽

Fine Tuning ◽

C2c12 Cells ◽

Transient Receptor Potential Vanilloid ◽

Membrane Polarization ◽

Transient Receptor

Anomalies in constitutive calcium entry (CCE) have been commonly attributed to cell dysfunction in pathological conditions such as cancer. Calcium influxes of this type rely on channels, such as transient receptor potential (TRP) channels, to be constitutively opened and strongly depend on membrane potential and a calcium driving force. We developed an optogenetic approach based on the expression of the halorhodopsin chloride pump to study CCE in non-excitable cells. Using C2C12 cells, we found that halorhodopsin can be used to achieve a finely tuned control of membrane polarization. Escalating the membrane polarization by incremental changes in light led to a concomitant increase in CCE through transient receptor potential vanilloid 2 (TRPV2) channels. Moreover, light-induced calcium entry through TRPV2 channels promoted cell migration. Our study shows for the first time that by modulating CCE and related physiological responses, such as cell motility, halorhodopsin serves as a potentially powerful tool that could open new avenues for the study of CCE and associated cellular behaviors.

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Role of Known Transient Receptor Potential Vanilloid Channels in Modulating Cardiac Mechanobiology

Frontiers in Physiology ◽

10.3389/fphys.2021.734113 ◽

2021 ◽

Vol 12 ◽

Author(s):

Michael Miller ◽

Sheryl E. Koch ◽

Adam Veteto ◽

Timothy Domeier ◽

Jack Rubinstein

Keyword(s):

Transient Receptor Potential ◽

Trp Channels ◽

Pressure Overload ◽

Receptor Potential ◽

Transient Receptor Potential Vanilloid ◽

Functional Responses ◽

Functional Protein ◽

Trpv Channels ◽

Transient Receptor ◽

And Function

The transient receptor potential (TRP) channels have been described in almost every mammalian cell type. Several members of the Vanilloid (TRPV) subtype have been found to play important roles in modulating cardiac structure and function through Ca2+ handling in response to systemic and local mechanobiological cues. In this review, we will consider the most studied TRPV channels in the cardiovascular field; transient receptor potential vanilloid 1 as a modulator of cardiac hypertrophy; transient receptor potential vanilloid 2 as a structural and functional protein; transient receptor potential vanilloid 3 in the development of hypertrophy and myocardial fibrosis; and transient receptor potential vanilloid 4 in its roles modulating the fibrotic and functional responses of the heart to pressure overload. Lastly, we will also review the potential overlapping roles of these channels with other TRP proteins as well as the advances in translational and clinical arenas associated with TRPV channels.

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Transient Receptor Potential Channels and Botulinum Neurotoxins in Chronic Pain

Frontiers in Molecular Neuroscience ◽

10.3389/fnmol.2021.772719 ◽

2021 ◽

Vol 14 ◽

Author(s):

Eun Jin Go ◽

Jeongkyu Ji ◽

Yong Ho Kim ◽

Temugin Berta ◽

Chul-Kyu Park

Keyword(s):

Chronic Pain ◽

Transient Receptor Potential ◽

Trp Channels ◽

Receptor Potential ◽

Transient Receptor Potential Channels ◽

Analgesic Effects ◽

Botulinum Neurotoxins ◽

Potential Channels ◽

Transient Receptor ◽

And Function

Pain afflicts more than 1.5 billion people worldwide, with hundreds of millions suffering from unrelieved chronic pain. Despite widespread recognition of the importance of developing better interventions for the relief of chronic pain, little is known about the mechanisms underlying this condition. However, transient receptor potential (TRP) ion channels in nociceptors have been shown to be essential players in the generation and progression of pain and have attracted the attention of several pharmaceutical companies as therapeutic targets. Unfortunately, TRP channel inhibitors have failed in clinical trials, at least in part due to their thermoregulatory function. Botulinum neurotoxins (BoNTs) have emerged as novel and safe pain therapeutics because of their regulation of exocytosis and pro-nociceptive neurotransmitters. However, it is becoming evident that BoNTs also regulate the expression and function of TRP channels, which may explain their analgesic effects. Here, we summarize the roles of TRP channels in pain, with a particular focus on TRPV1 and TRPA1, their regulation by BoNTs, and briefly discuss the use of BoNTs for the treatment of chronic pain.

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Faculty Opinions recommendation of Modular thermal sensors in temperature-gated transient receptor potential (TRP) channels.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.11817957.12914055 ◽

2011 ◽

Author(s):

Michael Andresen

Keyword(s):

Transient Receptor Potential ◽

Trp Channels ◽

Receptor Potential ◽

Thermal Sensors ◽

Transient Receptor

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Faculty Opinions recommendation of Activation of host transient receptor potential (TRP) channels by praziquantel stereoisomers.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.733074632.793545164 ◽

2018 ◽

Author(s):

David Triggle

Keyword(s):

Transient Receptor Potential ◽

Trp Channels ◽

Receptor Potential ◽

Transient Receptor

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TRPC1, TRPC3, and TRPC4 in Rat Orofacial Structures

Cells Tissues Organs ◽

10.1159/000477665 ◽

2017 ◽

Vol 204 (5-6) ◽

pp. 293-303 ◽

Cited By ~ 1

Author(s):

Masatoshi Fujita ◽

Tadasu Sato ◽

Takehiro Yajima ◽

Eiji Masaki ◽

Hiroyuki Ichikawa

Keyword(s):

Transient Receptor Potential ◽

Sympathetic Neurons ◽

Receptor Potential ◽

Monovalent Cation ◽

Calcitonin Gene ◽

Cervical Ganglion ◽

Parasympathetic Neurons ◽

Transient Receptor ◽

And Function ◽

And Control

TRPC (transient receptor potential cation channel subfamily C) members are nonselective monovalent cation channels and control Ca2+ inflow. In this study, immunohistochemistry for TRPC1, TRPC3, and TRPC4 was performed on rat oral and craniofacial structures to elucidate their distribution and function in the peripheries. In the trigeminal ganglion (TG), 56.1, 84.1, and 68.3% of sensory neurons were immunoreactive (IR) for TRPC1, TRPC3, and TRPC4, respectively. A double immunofluorescence method revealed that small to medium-sized TG neurons co-expressed TRPCs and calcitonin gene-related peptide. In the superior cervical ganglion, all sympathetic neurons showed TRPC1 and TRPC3 immunoreactivity. Parasympathetic neurons in the submandibular ganglion, tongue, and parotid gland were TRPC1, TRPC3, and TRPC4 IR. Gustatory and olfactory cells were also IR for TRPC1, TRPC3, and/or TRPC4. In the musculature, motor endplates expressed TRPC1 and TRPC4 immunoreactivity. It is likely that TRPCs are associated with sensory, autonomic, and motor functions in oral and craniofacial structures.

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Intragastric administration of capsiate, a transient receptor potential channel agonist, triggers thermogenic sympathetic responses

Journal of Applied Physiology ◽

10.1152/japplphysiol.00128.2010 ◽

2011 ◽

Vol 110 (3) ◽

pp. 789-798 ◽

Cited By ~ 68

Author(s):

Kaori Ono ◽

Masako Tsukamoto-Yasui ◽

Yoshiko Hara-Kimura ◽

Naohiko Inoue ◽

Yoshihito Nogusa ◽

...

Keyword(s):

Sympathetic Nerve ◽

Transient Receptor Potential ◽

Trp Channels ◽

Low Frequency ◽

Receptor Potential ◽

Transient Receptor Potential Channel ◽

Intragastric Administration ◽

Brown Adipose ◽

Reflex Arc ◽

Transient Receptor

The sympathetic thermoregulatory system controls the magnitude of adaptive thermogenesis in correspondence with the environmental temperature or the state of energy intake and plays a key role in determining the resultant energy storage. However, the nature of the trigger initiating this reflex arc remains to be determined. Here, using capsiate, a digestion-vulnerable capsaicin analog, we examined the involvement of specific activation of transient receptor potential (TRP) channels within the gastrointestinal tract in the thermogenic sympathetic system by measuring the efferent activity of the postganglionic sympathetic nerve innervating brown adipose tissue (BAT) in anesthetized rats. Intragastric administration of capsiate resulted in a time- and dose-dependent increase in integrated BAT sympathetic nerve activity (SNA) over 180 min, which was characterized by an emergence of sporadic high-activity phases composed of low-frequency bursts. This increase in BAT SNA was abolished by blockade of TRP channels as well as of sympathetic ganglionic transmission and was inhibited by ablation of the gastrointestinal vagus nerve. The activation of SNA was delimited to BAT and did not occur in the heart or pancreas. These results point to a neural pathway enabling the selective activation of the central network regulating the BAT SNA in response to a specific stimulation of gastrointestinal TRP channels and offer important implications for understanding the dietary-dependent regulation of energy metabolism and control of obesity.

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