Humans ; Ion Channels ; Pain ; Pressure ; TRPM Cation Channels ; TRPV Cation Channels ; Temperature

OBJECTIVE: To construct a three-dimensional structural model for the selectivity filter in the transient receptor pontential melastatin 8 (TRPM8) ion channel. METHODS: In the Rosetta computational structural biology suite, multiple rounds of modeling with the kinematic loop closure algorithm were performed. RESULTS: After nine rounds of computational modeling, we obtained the models of the selectivity filter within the TRPM8 channel with the lowest energy and high convergence. The model showed that the sidechain of D918 points were away from the central ion permeation pathway, while the sidechains of Q914, D920 and T923 pointed towards it. The glycosylation site N934 was located outside the pore region and its side chain directed to the extracellular water environment. CONCLUSIONS A three-dimensional structural model for the selectivity filter in the TRPM8 ion channel was constructed, which provides reliable structural information for exploring the mechanism of ion selectivity.
Algorithms ; Ion Channel Gating ; Models, Molecular ; TRPM Cation Channels ; chemistry

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

The transient receptor potential (TRP) family is a superfamily of cation channels located on the cell membrane. Transient receptor potential melastatin (TRPM) 7, a member of the TRPM subgroup of TRP channels, and was the most representative biofunctional membrane protein. It conducts calcium and monovalent cations to depolarize cells and increase intracellular calcium. It is capable of phosphorylating TRPM7 and other substrates. TRPM7 can mediate sensory transmission, regulate cellular Ca2+ and Mg2+ homeostasis and affect embryonic development. Abnormal expression and/or activity of the TRPM7 channel kinase is involved in a variety of diseases, particularly the development and progression of cancer. TRPM7 channel-kinase is essential for cellular processes, such as proliferation, survival, differentiation, growth, and migration.
Calcium ; Cell Differentiation ; Humans ; Neoplasms ; Protein-Serine-Threonine Kinases ; TRPM Cation Channels

OBJECTIVE: To explore the molecular pathogenesis for a pedigree affected with hypocalcemia secondary to hypomagnesemia. METHODS: Sanger sequencing was used to detect potential variant of the TRPM6 gene in the patient and their parents. RESULTS: The results showed that the patient has carried novel homozygous c.3311C>T (p.Pro1104Leu) variant of the TRMP6 gene, for which both of his parents were heterozygous carriers. Analysis of protein functions using software predicted high risk of pathogenicity. CONCLUSION The homozygous c.3311C>T (p.Pro1104Leu) variant of the TRPM6 gene probably underlies the disease in this patient.
Heterozygote ; Humans ; Hypocalcemia ; genetics ; Magnesium ; Magnesium Deficiency ; genetics ; Male ; Pedigree ; TRPM Cation Channels ; genetics

Transient receptor potential (TRP) channel is a superfamily of cation channels located on the cell membrane. TRP channels are classified into seven subfamilies based on the amino acid sequence homology,and transient receptor potential melastatin 2(TRPM2) is the second member of the TRPM subfamily. More evidences have revealed the important roles of TRPM2 in physiological and pathological events such as release of insulin from pancreatic Β-cells,inflammatory cytokines production from cells,and oxidative stress-induced cell death. As a cellular sensor for oxidative stress channel,TRPM2 is activated by a variety of factors. TRPM2 is a potential therapeutic target for oxidative stress-related diseases.
Cell Death ; Cytokines ; Humans ; Insulin ; Oxidative Stress ; TRPM Cation Channels ; physiology

Humans ; Brain Ischemia/therapy* ; Ischemic Stroke ; Receptors, N-Methyl-D-Aspartate ; TRPM Cation Channels

Cl(-) channel has been identified in heart over more than a decade. It is now known that Cl(-) channel is a super-family. The potentially important roles of cardiac Cl(-) channels have been emerging. Cardiac Cl(-) channels may play multifunctional roles in both physiological and pathophysiological conditions. Since the existence and distribution of cardiac Cl(-) channels vary with species and cardiac tissues, and blockade of Cl (-) channel with putative Cl(-) channel blockers or Cl(-) substitution has profound influence on cardiac electrical properties, it appears that the main role of cardiac Cl(-) channels may be to modulate cation channels or provide an ionic environment suitable for the activities of cation channels. So, to investigate the relationship between Cl(-) channels and cation channels may be of physiological and pathophysiological significance.
Animals ; Calcium Channels ; physiology ; Cations ; metabolism ; Chloride Channels ; physiology ; Heart ; physiology ; Humans ; Potassium Channels ; physiology ; Sodium Channels ; physiology ; TRPM Cation Channels ; physiology

OBJECTIVETo study the effects of the ingredients from Chinese herbs with the nature of cold or hot on the expression of TRPV1 and TRPM8.

METHODThe effects of ingredients from herbs on primary culture DRG neurons are observed in vitro. The expression quantity of gene is detected by the method of real time PCR. the 2 (-deltadeltaCT) method is applied to analyze the data.

RESULTIngredients from herbs with the nature of cold up-regulate the expression level of TRPV1 and down-regulate that of TRPM8, especially under the temperature condition of 39 degrees C; while ingredients from herbs with the nature of hot up-regulate the expression level of TRPM8 and down-regulated that of TRPV1, which is more significant under the temperature condition of 19 degrees C.

CONCLUSIONThe regulatory changes of TRPV1 and TRPM8 mRNA expression induced by the chemical ingredients might be related to the cold and hot natures of the herbs from which the ingredients are extracted. And this could be one of the therapeutic mechanisms for the treatment of Chinese herbal medicines to cold- and heat-related diseases.

Animals ; Drugs, Chinese Herbal ; administration & dosage ; analysis ; Gene Expression ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; TRPM Cation Channels ; genetics ; metabolism ; TRPV Cation Channels ; genetics ; metabolism

OBJECTIVETo study the expression of the mRNAs of transient receptor potential (TRP) gene subfamily TRPV and TRPM in rat testes.

METHODSNormal SD rat testes were collected and the expression of TRPV and TRPM mRNAs were detected by routine RT-PCR.

RESULTSThe TRPV4, TRPV5, TRPV6, TRPM3, TRPM4 and TRPM8 mRNAs were detected in the rat testes, but the other members of TRPV and TRPM family were not detected.

CONCLUSIONSTRPV4, TRPV5, TRPV6, TRPM3, TRPM4 and TRPM8 are expressed in rat testes. This finding provides the basis for exploring the functions of TRPV and TRPM in the testes and the relation between testis diseases and the TRP family.

Animals ; Male ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; TRPM Cation Channels ; genetics ; metabolism ; TRPV Cation Channels ; genetics ; metabolism ; Testis ; metabolism