Volume 100 Issue 2, February 2020

Transient receptor ion channels have emerged as critical channels/receptors in numerous physiological and pathological conditions. In this paper the authors discuss our current understanding of the role of macrophage transient receptor potential channel subfamily V member 4 (TRPV4) in various inflammatory conditions.

Transient receptor potential cation channel subfamily V (TRPV) can be overexpressed in breast cancer. TRPV channels play important roles in breast cancer cell proliferation, migration, and cell death as well as the tumor microenvironment and cancer-associated pain. This review provides an overview of TRPV channels in the context of breast cancer.

Transient receptor potential vanilloid 2 (TRPV2) plays a significant role in the onset and progression of heart failure. In this review, the authors summarize the recent findings on TRPV2 in cardiomyocytes and immune cells involved in the development of heart failure and discuss the current progress of drug development that is aimed at treating heart failure through targeting TRPV2.

The authors review the data which describe how the deletion of TRPV4 evokes abnormal behavior in mice. These studies demonstrate that the maintenance of body temperature and the sensory system for detecting body temperature, such as via TRPV4, are critical components for normal cellular function.

The calcium signal is a regulator of the acquisition of a more mesenchymal phenotype. Our work in MDA-MB-468 breast cancer cells identifies a complex relationship between factor-specific induction of the epithelial–mesenchymal marker vimentin and the differential involvement of the canonical store-operated calcium channel ORAI1 and the calcium channel component TRPC1.

Acute kidney injury and endothelial hyperpermeability are main features observed during severe sepsis with low survival rate. Transient receptor potential melastatin 7 (TRPM7) calcium channel inhibition protects against endotoxemia-induced kidney injury potentially by means of endothelial hyperpermeability decreasing. Remarkably, TRPM7 inhibition improves survival in endotoxemic animals.

The Niemann–Pick C1-like intracellular cholesterol transporter gene and a number of genes in the cholesterol synthesis pathway are transcriptionally regulated by SREBP-2. The liganded Ah receptor increases proteolytic turnover of transcriptionally active SREBP2. Thus, Ah receptor ligands are capable of attenuating cholesterol uptake into Caco-2 cells.

Allergic asthma is one of the most common immune-mediated disorders. The authors investigated the possibility that TPRV4 cation channels facilitate the development of allergic asthma and subsequent pulmonary fibrosis in the lung. Their data suggest that TPRV4 is dispensable in the initiation and development of airway asthma and subsequent fibrosis.

The authors reveal that TRPV4, a thermosensitive ion channel, is constitutively active in the brain. They found that local brain temperature is increased at epileptogenic foci, and that hyperthermia lead TRPV4 over-activation and hyper-neuronal activities. Notably, brain cooling treatment drastically suppresses epileptic discharges dependent on the inactivation of TRPV4.

Vascular endothelial growth factor increases the profibrotic activity of atrial fibroblasts by activating the currents through transient receptor potential channels and intermediate-conductance calcium-activated K⁺ (K_Ca3.1) channels and by enhancing Ca²⁺ entry-induced phosphorylated Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) signaling. These findings suggest a novel strategy targeting atrial myopathy and arrhythmofibrosis.

This study shows that TRPC5 is an important negative regulator of retinal ganglion cell (RGC) axonal outgrowth and an important regulator of neurite remodeling. The authors hypothesize that TRPC5 senses abnormal intraocular pressure changes and contributes to the death of RGCs in disease. In glaucoma, for example, excessive Ca2+ entry through TRPC5 might induce dendritic and axonal remodeling, which could lead to cell death.

This paper shows that TRPV4, a Ca²⁺-permeable nonselective cation channel, responds to extracellular environments to regulate oral squamous cell carcinoma cellular growth through CaMKII/AKT activity in vitro and in vivo.

The authors generated a functional monoclonal antibody that recognizes and promotes the internalization of TRPV2 to reduce TRPV2-driven Ca²⁺ influx. Using cardiomyopathic/muscular dystrophic animal models, they confirmed the beneficial effects of this antibody, which includes improvements in both Ca²⁺ handling in cardiomyocytes and in skeletal muscle properties.