Transient receptor potential M2 (TRPM2) ion channel is a non-selective cationic channel that can permeate calcium ions, and plays an important role in neuroinflammation, ischemic reperfusion brain injury, neurodegenerative disease, neuropathic pain, epilepsy and other neurological diseases. In ischemic reperfusion brain injury, TRPM2 mediates neuronal death by modulating the different subunits of glutamate N-methyl-D-aspartic acid receptor in response to calcium/zinc signal. In Alzheimer's disease, TRPM2 is activated by reactive oxygen species generated by β-amyloid peptide to form a malignant positive feedback loop that induces neuronal death and is involved in the pathological process of glial cells by promoting inflammatory response and oxidative stress. In epilepsy, the TRPM2-knockout alleviates epilepsy induced neuronal degeneration by inhibiting autophagy and apoptosis related proteins. The roles of TRPM2 channel in the pathogenesis of various central nervous system diseases and its potential drug development and clinical application prospects are summarized in this review.
Amyloid beta-Peptides/metabolism* ; Humans ; Neurodegenerative Diseases ; Neuroglia ; TRPM Cation Channels/genetics* ; Transient Receptor Potential Channels

OBJECTIVES: To investigate the role of transient receptor potential cation channel subfamily M member 2 (TRPM2) in hepatic ischemia-reperfusion injury of mouse (HIRI) and the possible mechanisms. METHODS: Sixty adult male C57BL/6 mice were randomly divided into 4 groups: a sham group (S group), a HIRI model group (M group), a TRPM2 adenovirus interference vector group (T group), and a TRPM2 adenovirus control vector group (C group) (=15 in each group). The liver tissues of mice before perfusion were obtained. The efficiency of adenovirus infection was detected by fluorescence microscopy, and the silencing efficiency of adenovirus against TRPM2 was detected by real-time PCR.The abdominal aorta blood and liver tissues were collected from mice at 2, 4 and 8 h after reperfusion. The activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum of mice were detected. Hepatic pathological changes were examined by hematoxylin-eosin (HE) staining. The protein expression of TRPM2 and Rac family small GTPase 1 (RAC1) in liver tissues was detected by Western blotting. Changes of malondialdehyde (MDA), superoxide dismutase (SOD) and myeloperoxidase (MPO) activities in liver tissues were detected by enzyme-linked immunosorbent assay. RESULTS: A strong signal of green fluorescence was observed in the liver tissues of mice in the T and C groups compared to the S or M group. Compared with the S, M or C group, the expression of TRPM2 mRNA in liver tissue in the T group was significantly down-regulated (all <0.05). The morphology of hepatocytes was normal in the S group under light microscope.Hepatic sinus dilatation, congestion, hepatocyte degeneration, central necrosis of lobule, and massive inflammatory granulocyte infiltration were observed in the M and C group, respectively. The degree of hepatocyte damage in the T group was significantly reduced compared with that in the M and C group, respectively. Compared with the S group, the serum ALT and AST activities in the M, T and C groups were significantly increased at 2, 4 and 8 h after reperfusion (all <0.05). Compared with the M or C group, the serum ALT and AST activities in the T group were significantly lower in serum of mice at 2, 4, and 8 h after reperfusion (all <0.05). Compared with the M or C group, the serum SOD activity in the T group was significantly increased at 2, 4, and 8 h after reperfusion (all <0.05), while the serum MDA and MPO activities were significantly decreased (all <0.05). The protein expression of TRPM2 and RAC1 in liver tissues in the T group were significantly lower than those in the M and C groups at 2, 4 and 8 h after reperfusion (all <0.05). CONCLUSIONS Pretreatment with TRPM2 adenovirus interference vector can effectively silence TRPM2 gene expression in liver tissues of mice and attenuate HIRI, which may be related to inhibiting oxidative stress and reducing the expression of RAC1 protein.
Alanine Transaminase ; Animals ; Aspartate Aminotransferases ; Liver ; Male ; Mice ; Mice, Inbred C57BL ; Neuropeptides ; Rats, Sprague-Dawley ; Reperfusion Injury ; TRPM Cation Channels ; genetics ; Transient Receptor Potential Channels ; rac1 GTP-Binding Protein

Humans ; Hypertension ; metabolism ; pathology ; Transient Receptor Potential Channels ; metabolism ; physiology

Transient receptor potential (TRP) channels, a large family of receptor channel proteins, initially attracted researchers in the pain field as key molecules in nociception, but later they became known as more general transducer molecules for various physical stresses. In this review, I will discuss their roles in thermal and mechanical sensation, and then consider their contribution to physiological pain.
Humans ; Nociception ; Proteins ; Sensation ; Transducers ; Transient Receptor Potential Channels

Artemin is a neuronal survival and differentiation factor in the glial cell line-derived neurotrophic factor family. Its receptor GFRalpha3 is expressed by a subpopulation of nociceptor type sensory neurons in the dorsal root and trigeminal ganglia (DRG and TG). These neurons co-express the heat, capsaicin and proton-sensitive channel TRPV1 and the cold and chemical-sensitive channel TRPA1. To further investigate the effects of artemin on sensory neurons, we isolated transgenic mice (ARTN-OE mice) that overexpress artemin in keratinocytes of the skin and tongue. Enhanced levels of artemin led to a 20% increase in the total number of DRG neurons and increases in the level of mRNA encoding TRPV1 and TRPA1. Calcium imaging showed that isolated sensory neurons from ARTN-OE mice were hypersensitive to the TRPV1 agonist capsaicin and the TRPA1 agonist mustard oil. Behavioral testing of ARTN-OE mice also showed an increased sensitivity to heat, cold, capsaicin and mustard oil stimuli applied either to the skin or in the drinking water. Sensory neurons from wildtype mice also exhibited potentiated capsaicin responses following artemin addition to the media. In addition, injection of artemin into hindpaw skin produced transient thermal hyperalgesia. These findings indicate that artemin can modulate sensory function and that this regulation may occur through changes in channel gene expression. Because artemin mRNA expression is up-regulated in inflamed tissue and following nerve injury, it may have a significant role in cellular changes that underlie pain associated with pathological conditions. Manipulation of artemin expression may therefore offer a new pain treatment strategy.
Animals ; Hot Temperature ; Hyperalgesia ; metabolism ; Keratinocytes ; physiology ; Mice ; Mice, Transgenic ; Nerve Tissue Proteins ; genetics ; metabolism ; Nociceptors ; physiology ; Skin ; cytology ; TRPA1 Cation Channel ; TRPV Cation Channels ; metabolism ; Tongue ; cytology ; Transient Receptor Potential Channels ; metabolism

Injury or inflammation induces release of a range of inflammatory mediators. Bradykinin is one of the most important inflammatory mediators and plays a crucial role in mediating inflammatory pain. It is well known that multiple ion channels located in the nociceptors participate in pain sensation. Recent studies demonstrate an important role of bradykinin in regulating the function and expression of pain-related ion channels. This paper summarizes the recent advances in the understanding of the role of bradykinin in modulation of the channels and discusses future possibilities in the treatment of inflammatory pain.
Acid Sensing Ion Channels ; Animals ; Bradykinin ; pharmacology ; physiology ; Humans ; Inflammation ; complications ; Inflammation Mediators ; pharmacology ; physiology ; Ion Channels ; KCNQ Potassium Channels ; metabolism ; physiology ; Nerve Tissue Proteins ; metabolism ; Pain ; etiology ; metabolism ; physiopathology ; Receptors, AMPA ; metabolism ; Receptors, N-Methyl-D-Aspartate ; metabolism ; Receptors, Purinergic P2X3 ; metabolism ; Sodium Channels ; metabolism ; TRPA1 Cation Channel ; TRPV Cation Channels ; metabolism ; physiology ; Transient Receptor Potential Channels ; metabolism ; physiology

Transient receptor potential (TRP) ion channels are widely distributed in different kinds of cells. TRP expresses highly in the prostatic cancer epithelia at different levels, but whether it expresses in chronic prostatitis epithelia or not remains poorly understood. Investigating the roles of TRP ion channels in the pathogenesis of prostatic diseases could afford us a new approach to their diagnosis and therapy.
Calcium Channels ; Calcium Signaling ; Humans ; Male ; Prostatic Diseases ; metabolism ; pathology ; Transient Receptor Potential Channels

During membrane depolarization associated with skeletal excitation-contraction (EC) coupling, dihydropyridine receptor [DHPR, a L-type Ca2+ channel in the transverse (t)-tubule membrane] undergoes conformational changes that are transmitted to ryanodine receptor 1 [RyR1, an internal Ca2+-release channel in the sarcoplasmic reticulum (SR) membrane] causing Ca2+ release from the SR. Canonical-type transient receptor potential cation channel 3 (TRPC3), an extracellular Ca2+-entry channel in the t-tubule and plasma membrane, is required for full-gain of skeletal EC coupling. To examine additional role(s) for TRPC3 in skeletal muscle other than mediation of EC coupling, in the present study, we created a stable myoblast line with reduced TRPC3 expression and without alpha1SDHPR (MDG/TRPC3 KD myoblast) by knock-down of TRPC3 in alpha1SDHPR-null muscular dysgenic (MDG) myoblasts using retrovirus-delivered small interference RNAs in order to eliminate any DHPR-associated EC coupling-related events. Unlike wild-type or alpha1SDHPR-null MDG myoblasts, MDG/TRPC3 KD myoblasts exhibited dramatic changes in cellular morphology (e.g., unusual expansion of both cell volume and the plasma membrane, and multi-nuclei) and failed to differentiate into myotubes possibly due to increased Ca2+ content in the SR. These results suggest that TRPC3 plays an important role in the maintenance of skeletal muscle myoblasts and myotubes.
Animals ; Calcium/metabolism ; Calcium Channels/metabolism ; Calcium Channels, L-Type/genetics/metabolism ; Cations/metabolism ; *Cell Differentiation ; *Cell Proliferation ; Cells, Cultured ; Excitation Contraction Coupling ; Gene Knockdown Techniques ; Membrane Potentials ; Mice ; Muscle Fibers, Skeletal/*metabolism ; Muscle Proteins/metabolism ; Myoblasts, Skeletal/*metabolism ; Ryanodine Receptor Calcium Release Channel/metabolism ; Sarcoplasmic Reticulum/*physiology ; Synaptophysin/metabolism ; TRPC Cation Channels/genetics/*metabolism ; Transient Receptor Potential Channels/metabolism

Channels from the TRP superfamily have essential roles in a wide variety of sensory transductions, especially in mechano-sensation, such as hearing, touch and mechanical pain. TRP channels are also implicated in major channelopathies, including deafness, chronic pain, autosomal dominant polycystic kidney disease (ADPKD) and ventricular hypertrophy. As the leading candidates for mechano-sensitive channels, some TRP channels appear to be mechano-receptor, which can be activated by mechanical forces directly, such as C. elegans TRPN homolog TRP-4; whereas others may act as signal modulators, receiving and amplifying signals indirectly. This review is to introduce the function of TRPs in mechano-sensory transduction and to discuss the underlying molecular mechanisms.
Animals ; Humans ; Neural Conduction ; Sensation ; physiology ; Signal Transduction ; Transient Receptor Potential Channels ; metabolism ; physiology

OBJECTIVE: To observe the effect of Miao medicinal acupuncture therapy on transient receptor potential vanilloid (TRPV) channel in knee joint synovial tissue of the rabbits with knee osteoarthritis (KOA) model and to explore the mechanism of Miao medicinal acupuncture therapy in treatment of KOA. METHODS: Of 34 New Zealand male rabbits, 6 rabbits were selected randomly as the normal group. KOA model was established in the rest rabbits by injecting a mixture of papain and L-cysteine in right knee joints. The 24 successfully modeled rabbits were randomized into a model group, a Miao medicinal acupuncture therapy group, a dermal needle group and a smearing group, 6 rabbits in each one. In the Miao medicinal acupuncture therapy group, Miao medicinal acupuncture therapy was adopted, in which, the roller type of dermal needle was used on the surface of right knee joint [a rectangle shape formed by "Xuehai" (SP 10), "Liangqiu" (ST 34), "Yanglingquan" (GB 34) and "Yinlingquan" (SP 9)], rolling in a " shape, on which, Miao medicinal solution was smeared in advance. In the dermal needle group, the rolling stimulation was exerted on the right the right knee joint surface with the roller type of dermal needle. In the smearing group, Miao medicinal solution was smeared on the right knee joint surface. The intervention was given once every two days, 3 times weekly and the intervention was exerted consecutively for 4 weeks. Successively, on day 1, 21, 28, 35, 42 and 49 of experiment, paw withdrawal threshold (von Frey threshold) after mechanical stimulation was detected in the rabbits. HE staining was adopted to observe the histomorphological changes of the right knee joint cartilage in the rabbits. ELISA was used to determine the contents of interleukin-1 (IL-1β) and tumor necrosis factor-α (TNF-α) in the right knee synovial fluid. Western blot method and real-time PCR were used to determine the relative expressions of protein and mRNA of TRPV1 and TRPV4 in knee synovial tissue of the rabbits. RESULTS: Compared with the normal group, on day 49 of experiment, von Frey threshold was reduced significantly in the rabbits of the model group ( CONCLUSION Miao medicinal acupuncture therapy plays a role in treatment of KOA probably through inhibiting the expressions of IL-1β and TNF-α of knee synovial fluid and down-regulating the expressions of protein and mRNA of TRPV1 and TRPV4 in knee synovial tissue.
Acupuncture Therapy ; Animals ; Knee Joint ; Male ; Osteoarthritis, Knee/therapy* ; Rabbits ; Synovial Fluid ; Transient Receptor Potential Channels