Modulation of the cold-activated cation channel TRPM8 by surface charge screening.

TRPM8, a cation channel activated by cold and by cooling agents such as menthol and icilin, is critically involved in somatosensory cold sensation. Ion fluxes through TRPM8 are highly sensitive to changes in extracellular Ca(2+) and pH, but the mechanisms underlying this type of modulation are poorly understood. Here we provide evidence that inhibition of TRPM8 currents by extracellular divalent cations and protons is due to surface charge screening.

HGF/SF and menthol increase human glioblastoma cell calcium and migration.

This study explored the role of transient receptor potential melastatin 8 ion channels (TRPM8) in mechanisms of human glioblastoma (DBTRG) cell migration. Menthol stimulated influx of Ca(2+), membrane current, and migration of DBTRG cells. Effects on Ca(2+) and migration were enhanced by pre-treatment with hepatocyte growth factor/scatter factor (HGF/SF).

TRPM8-independent menthol-induced Ca2+ release from endoplasmic reticulum and Golgi.

Menthol, a secondary alcohol produced by the peppermint herb, Mentha piperita, is widely used in the food and pharmaceutical industries as a cooling/soothing compound and odorant. It induces Ca2+ influx in a subset of sensory neurons from dorsal root and trigeminal ganglia, due to activation of TRPM8, a Ca2+-permeable, cold-activated member of the TRP superfamily of cation channels. Menthol also induces Ca2+ release from intracellular stores in several TRPM8-expressing cell types, which has led to the suggestion that TRPM8 can function as an intracellular Ca2+-release channel.

Calbindin-D28K dynamically controls TRPV5-mediated Ca2+ transport.

In Ca(2+)-transporting epithelia, calbindin-D(28K) (CaBP(28K)) facilitates Ca(2+) diffusion from the luminal Ca(2+) entry side of the cell to the basolateral side, where Ca(2+) is extruded into the extracellular compartment. Simultaneously, CaBP(28K) provides protection against toxic high Ca(2+) levels by buffering the cytosolic Ca(2+) concentration ([Ca(2+)](i)) during high Ca(2+) influx. CaBP(28K) consistently colocalizes with the epithelial Ca(2+) channel TRPV5, which constitutes the apical entry step in renal Ca(2+)-transporting epithelial cells.

A road map for TR(I)Ps.

The development of our knowledge on the structure, molecular regulation, and cell function on transient receptor potential (TRP) channels has been growing dramatically during the last few years. Many meetings in the past and upcoming events are now focused on TRP channels as general sensor molecules in cell physiology. However, most of the scientists in the field still feel that we are just beginning to understand these truly remarkable proteins, called TRPs, and there is still a long way to go from structure via molecular regulation to cell and organ function.

The Ca2+-activated cation channel TRPM4 is regulated by phosphatidylinositol 4,5-biphosphate.

Transient receptor potential (TRP) channel, melastatin subfamily (TRPM)4 is a Ca2+-activated monovalent cation channel that depolarizes the plasma membrane and thereby modulates Ca2+ influx through Ca2+-permeable pathways. A typical feature of TRPM4 is its rapid desensitization to intracellular Ca2+ ([Ca2+]i). Here we show that phosphatidylinositol 4,5-biphosphate (PIP2) counteracts desensitization to [Ca2+]i in inside-out patches and rundown of TRPM4 currents in whole-cell patch-clamp experiments.

80K-H as a new Ca2+ sensor regulating the activity of the epithelial Ca2+ channel transient receptor potential cation channel V5 (TRPV5).

The epithelial Ca(2+) channel transient receptor potential cation channel V5 (TRPV5) constitutes the apical Ca(2+) entry pathway in the process of active Ca(2+) reabsorption. Ca(2+) influx through TRPV5 is tightly controlled by modulators of Ca(2+) homeostasis, including 1,25-dihydroxyvitamin D(3) and dietary Ca(2+). However, little is known about intracellular proteins that interact with TRPV5 and directly regulate the activation of this channel.

Microbial Toll-like receptor ligands differentially regulate CXCL10/IP-10 expression in fibroblasts and mononuclear leukocytes in synergy with IFN-gamma and provide a mechanism for enhanced synovial chemokine levels in septic arthritis.

The CXC chemokine IFN-gamma-inducible protein-10 (IP-10/CXCL10) activates CXC chemokine receptor 3 (CXCR3) and attracts activated T cells and natural killer cells. Peripheral blood mononuclear cells (PBMC) produce low but significant amounts of IP-10/CXCL10 protein upon stimulation with double-stranded (ds) RNA, the Toll-like receptor 3 (TLR3) ligand. IFN-gamma is a superior IP-10/CXCL10inducer.

The unique property of the CC chemokine regakine-1 to synergize with other plasma-derived inflammatory mediators in neutrophil chemotaxis does not reside in its NH2-terminal structure.

The recently discovered CC chemokine, regakine-1, is constitutively present in bovine serum and synergizes with the CXC chemokine interleukin-8 (IL-8) to chemoattract neutrophils. Here we show that regakine-1 cooperates with the CXC chemokine receptor 2 ligand neutrophil activating protein-2 (NAP-2) and the anaphylatoxin C5a, two other mediators of inflammation present in the circulation. Neutrophil chemotaxis was 3-fold enhanced when regakine-1 (100 ng/ml) and C5a (30 ng/ml) were combined at concentrations present in bovine or human plasma, respectively.