• The Korean Journal of Physiology and Pharmacology
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• v.24 no.1
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• pp.101-110
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• 2020

Transient receptor potential canonical 4 (TRPC4) channel is a nonselective calcium-permeable cation channels. In intestinal smooth muscle cells, TRPC4 currents contribute more than 80% to muscarinic cationic current (mIcat). With its inward-rectifying current-voltage relationship and high calcium permeability, TRPC4 channels permit calcium influx once the channel is opened by muscarinic receptor stimulation. Polyamines are known to inhibit nonselective cation channels that mediate the generation of mIcat. Moreover, it is reported that TRPC4 channels are blocked by the intracellular spermine through electrostatic interaction with glutamate residues (E728, E729). Here, we investigated the correlation between the magnitude of channel inactivation by spermine and the magnitude of channel conductance. We also found additional spermine binding sites in TRPC4. We evaluated channel activity with electrophysiological recordings and revalidated structural significance based on Cryo-EM structure, which was resolved recently. We found that there is no correlation between magnitude of inhibitory action of spermine and magnitude of maximum current of the channel. In intracellular region, TRPC4 attracts spermine at channel periphery by reducing access resistance, and acidic residues contribute to blocking action of intracellular spermine; channel periphery, E649; cytosolic space, D629, D649, and E687.

• The Korean Journal of Physiology and Pharmacology
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• v.11 no.5
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• pp.227-231
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• 2007

The classic type of transient receptor potential channel(TRPC) is a molecular candidate for $Ca^{2+}$-permeable cation channel in mammalian cells. TRPC5 is rapidly desensitized after activation by G protein-coupled receptor. Herein we report the effect of dimethyl sulfoxide(DMSO) on the desensitization of TRPC5. TRPC5 was initially activated by muscarinic stimulation with $50{\mu}M$ carbachol(CCh) and then decayed rapidly even in the presence of CCh(desensitization). DMSO in the pipette solution slowed the rate of this desensitization. Under the control conditions, TRPC5 current spontaneously declined to $6{\pm}1%$ of the initial peak amplitude 60 sec after CCh application and to $1{\pm}0.5%$ after 120 sec. But, in the presence of 0.01%, 0.1% and 1% DMSO, TRPC5 current spontaneously declined to $55{\pm}2%,\;68{\pm}1%\;and\;100{\pm}0.2%$ of the initial peak amplitude 60 sec after CCh application and to $38{\pm}2%,\;61{\pm}1%\;and\;100{\pm}1%$ after 120 see, respectively. The results suggest that DMSO can internally attenuate the desensitization of TRPC5 current through unknown mechanisms that remain to be elucidated.

• BMB Reports
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• v.37 no.1
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• pp.114-121
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• 2004

Ion channels of the transient receptor potential (TRP) superfamily are non-selective cationic channels with six transmembrane domains. The TRP channel made its first debut as a light-gated $Ca^{2+}$ channel in Drosophila. Recently, research on animal sensation in Drosophila disclosed other members of the TRP family that are required for touch sensation and hearing as well as the sensation of painful stimuli.

• Molecules and Cells
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• v.21 no.3
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• pp.315-329
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• 2006

Two, well characterized cationic channels, the ryanodine receptor (RyR) and the canonical transient receptor potential cation channel (TRPC) are briefly reviewed with a particular attention on recent developments related to the interplay between the two channel families.

• The Korean Journal of Pain
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• v.37 no.4
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• pp.299-309
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• 2024

Chronic peripheral neuropathic pain therapy currently focuses on modulating neuroinflammatory conditions. Methylcobalamin (MeCbl), a neuroregenerative agent, modulates neuroinflammation. This review aimed to explore the molecular pharmacology action of MeCbl as a chronic peripheral neuropathic pain therapeutic agent. MeCbl plays a role in various cellular processes and may have therapeutic potential in neurodegenerative diseases. Intracellular MeCbl modulates inflammation by regulating the activity of T lymphocytes and natural killer cells as well as secretion of inflammatory cytokines, namely, tumor necrosis factor-α, interleukin-6, interleukin-1β, epidermal growth factor, and neuronal growth factor. MeCbl can reduce pain symptoms in chronic neuropathic pain conditions by decreasing excitation and hyperpolarization-induced ion channel activity in medium-sized dorsal root ganglion (DRG) neurons and the expression of transient receptor potential ankyrin 1, transient receptor potential cation channel subfamily M member 8, phosphorylated p38MAPK, transient receptor potential cation channel subfamily V members 1 and 4 in the DRG, and the voltage-gated sodium channel in axons.

• Molecules and Cells
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• v.42 no.8
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• pp.569-578
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• 2019

Transient receptor potential (TRP) channels are nonselective cationic channels, conserved among flies to humans. Most TRP channels have well known functions in chemosensation, thermosensation, and mechanosensation. In addition to being sensing environmental changes, many TRP channels are also internal sensors that help maintain homeostasis. Recent improvements to analytical methods for genomics and metabolomics allow us to investigate these channels in both mutant animals and humans. In this review, we discuss three aspects of TRP channels, which are their role in metabolism, their functional characteristics, and their role in metabolic syndrome. First, we introduce each TRP channel superfamily and their particular roles in metabolism. Second, we provide evidence for which metabolites TRP channels affect, such as lipids or glucose. Third, we discuss correlations between TRP channels and obesity, diabetes, and mucolipidosis. The cellular metabolism of TRP channels gives us possible therapeutic approaches for an effective prophylaxis of metabolic syndromes.

• Journal of Medicine and Life Science
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• v.20 no.1
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• pp.1-7
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• 2023

Transient receptor potential ankyrin 1 (TRPA1) receptors are major polymodal nociceptors that generate primary pain responses in the peripheral nerve endings of the dorsal root ganglion neurons. Recently, we reported that the activation of TRPA1 receptors by reactive oxygen species (ROS) signaling, which is triggered by Ca²⁺ influx through T-type Ca²⁺ channels, contributes to prolonged pain responses induced by jellyfish toxin. In this review, we focus on the characteristics of the TRPA1 receptor involved in intracellular signaling as a secondary pain modulator. Unlike other transient receptor potential receptors, TRPA1 receptors can induce membrane depolarization by ROS without exogenous stimuli in peripheral and central sensory neurons. Therefore, it is important to identify the functional characteristics of TRPA1 receptors to understand pain modulation under several pathogenic conditions such as neuropathic pain syndromes and autoimmune diseases, which are mediated by oxidative signaling to cause chronic pain in the sensory system.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.2
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• pp.187-196
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• 2023

Transient receptor potential canonical (TRPC) channels are non-selective calcium-permeable cation channels. It is suggested that TRPC4β is regulated by phospholipase C (PLC) signaling and is especially maintained by phosphatidylinositol 4,5-bisphosphate (PIP₂). In this study, we present the regulation mechanism of the TRPC4 channel with PIP₂ hydrolysis which is mediated by a channel-bound PLCδ1 but not by the G_qPCR signaling pathway. Our electrophysiological recordings demonstrate that the Ca²⁺ via an open TRPC4 channel activates PLCδ1 in the physiological range, and it causes the decrease of current amplitude. The existence of PLCδ1 accelerated PIP₂ depletion when the channel was activated by an agonist. Interestingly, PLCδ1 mutants which have lost the ability to regulate PIP₂ level failed to reduce the TRPC4 current amplitude. Our results demonstrate that TRPC4 self-regulates its activity by allowing Ca²⁺ ions into the cell and promoting the PIP₂ hydrolyzing activity of PLCδ1.

• Journal of Ginseng Research
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• v.37 no.2
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• pp.201-209
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• 2013

Ginsenoside, one of the active ingredients of Panax ginseng, has a variety of physiologic and pharmacologic effects. The purpose of this study was to explore the effects of ginsenoside Rd (G-Rd) on melastatin type transient receptor potential 7 (TRPM7) channels with respect to the proliferation and survival of AGS and MCF-7 cells (a gastric and a breast cancer cell line, respectively). AGS and MCF-7 cells were treated with different concentrations of G-Rd, and caspase-3 activities, mitochondrial depolarizations, and sub-G1 fractions were analyzed to determine if cell death occurred by apoptosis. In addition, human embryonic kidney (HEK) 293 cells overexpressing TRPM7 channels were used to confirm the role of TRPM7 channels. G-Rd inhibited the proliferation and survival of AGS and MCF-7 cells and enhanced caspase-3 activity, mitochondrial depolarization, and sub-G1 populations. In addition, G-Rd inhibited TRPM7-like currents in AGS and MCF-7 cells and in TRPM7 channel overexpressing HEK 293 cells, as determined by whole cell voltage-clamp recordings. Furthermore, TRPM7 overexpression in HEK 293 cells promoted G-Rd induced cell death. These findings suggest that G-Rd inhibits the proliferation and survival of gastric and breast cancer cells by inhibiting TRPM7 channel activity.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.3
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• pp.191-201
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• 2019

The transient receptor potential canonical (TRPC) 5 channel, known as a nonselective cation channel, has a crucial role in calcium influx. TRPC5 has been reported to be activated by muscarinic receptor activation and extracellular pH change and inhibited by the protein kinase C pathway. Recent studies have also suggested that TRPC5 is extracellularly activated by englerin A (EA), but the mechanism remains unclear. The purpose of this study is to identify the EA-interaction sites in TRPC5 and thereby clarify the mechanism of TRPC5 activation. TRPC5 channels are over-expressed in human embryonic kidney (HEK293) cells. TRPC5 mutants were generated by site-directed mutagenesis. The whole-cell patch-clamp configuration was used to record TRPC5 currents. Western analysis was also performed to observe the expression of TRPC5 mutants. To identify the EA-interaction site in TRPC5, we first generated pore mutants. When screening the mutants with EA, we observed the EA-induced current increases of TRPC5 abolished in K554N, H594N, and E598Q mutants. The current increases of other mutants were reduced in different levels. We also examined the functional intactness of the mutants that had no effect by EA with TRPC5 agonists, such as carbachol or $GTP{\gamma}S$. Our results suggest that the three residues, Lys-554, His-594, and Glu-598, in TRPC5 might be responsible for direct interaction with EA, inducing the channel activation. We also suggest that although other pore residues are not critical, they could partly contribute to the EA-induced channel activation.