TRPC

The canonical transient receptor potential channel (TRPC) proteins form Ca2+ -permeable cation channels that are involved in various heart diseases. However, the roles of specific TRPC proteins in myocardial ischemia/reperfusion (I/R) injury remain poorly understood. We observed that TRPC1 and TRPC6 were highly expressed in the area at risk (AAR) in a coronary artery ligation induced I/R model. Trpc1 -/- mice exhibited improved cardiac function, lower serum Troponin T and serum creatine kinase level, smaller infarct volume, less fibrotic scars, and fewer apoptotic cells after myocardial-I/R than wild-type or Trpc6 -/- mice...

The mantis shrimp is the only animal that can recognize circularly polarized light (CPL), but its molecular genetic characteristics are unclear. Multi-tissue level full-length (FL) transcriptome sequencing of Oratosquilla oratoria, a representative widely distributed mantis shrimp, was performed in the present study. We used comparative transcriptomics to explore the critical genes of O. oratoria selected by CPL and the GNβ gene associated with CPL signal transduction was hypothesized to be positively selected...

Canonical transient receptor potential channels (TRPCs) are a family of calcium-permeable cation channels. Previous studies have shown that heteromeric channels comprising TRPC1 and TRPC4 mediate epileptiform bursting in lateral septal neurons and hippocampal CA1 pyramidal neurons, suggesting that TRPC1/4 channels play a pro-seizure role. In this study, we utilized electroencephalography (EEG) recording and spectral analysis to assess the role of TRPC1/4 channels in the pilocarpine model of status epilepticus (SE)...

Store-operated calcium entry (SOCE) in cardiomyocytes may be involved in cardiac remodeling, but the underlying mechanisms remain elusive. We hypothesized that SOCE may increase nuclear calcium, which alters gene expression via calcium/calmodulin-dependent enzyme signaling, and elucidated the underlying cellular mechanisms. An experimental protocol was established in isolated adult rat cardiomyocytes to elicit SOCE by re-addition of calcium following complete depletion of sarcoplasmic reticulum (SR) calcium and to quantify SOCE in relation to the electrically stimulated calcium transient (CaT) measured in the same cell before SR depletion...

Angiotensin Receptor blockers (ARBs) are the first-line treatment for hypertension; they act by inhibiting signaling through the angiotensin 1 receptor (AT1R). Recently, a novel biased AT1R agonist, TRV120027 (TRV), that selectively activates the β-arrestin cascade and blocks the G-protein-coupled receptor pathway has been proposed as a potential blood pressure medication. Here, we explored the effects of TRV and associated β-arrestin signaling in podocytes, essential cells of the kidney filter...

INTRODUCTION: Depression, anxiety, and/or panic disorder are often comorbid and have a complex etiology mediated through the same neuronal network. Cholecystokinin-tetrapeptide (CCK-4), a synthetic analog of the endogenous neuropeptide cholecystokinin (CCK), is thought to be implicated in this network. The CCK-4 challenge model is an accepted method of investigating the pathophysiology of panic and has been shown to mediate neuronal activation via the transient receptor potential canonical (TRPC) ion channels...

INTRODUCTION: The transient receptor potential canonical (TRPC) ion channels have been implicated in the pathophysiology of major depressive disorder (MDD), and TRPC inhibition has been shown to reduce depressive-like behaviour in rodent models of depression. BI 1358894, a small-molecule inhibitor of TRPC ion channels, is currently being developed for the treatment of MDD. OBJECTIVE: Two phase I studies assessed the safety, tolerability, and pharmacokinetics (PK) of oral BI 1358894 in fed and fasted states following a single ascending dose (SAD) [NCT03210272/1402-0001] and multiple ascending doses (MAD) [NCT03754959/1402-0002] in healthy male volunteers...

Excessive activation of the immune system is the cause of a wide variety of renal diseases. However, the pathogenic mechanisms underlying the aberrant activation of the immune system in the kidneys often remain unknown. TRPC6, a member of the Ca2+ -permeant family of TRPC channels, is important in glomerular epithelial cells or podocytes for the process of glomerular filtration. In addition, TRPC6 plays a crucial role in the development of kidney injuries by inducing podocyte injury. However, an increasing number of studies suggest that TRPC6 is also responsible for tightly regulating the immune cell functions...

Ischemic stroke is a devastating disease that affects millions of patients worldwide. Unfortunately, there are no effective medications for mitigating brain injury after ischemic stroke. TRP channels are evolutionally ancient biosensors that detect external stimuli as well as tissue or cellular injury. To date, many members of the TRP superfamily have been reported to contribute to ischemic brain injury, including the TRPC subfamily (1, 3, 4, 5, 6, 7), TRPV subfamily (1, 2, 3, 4) and TRPM subfamily (2, 4, 7)...

Transient receptor potential (TRP) ion channels are evolutionarily conserved integral membrane proteins with non-selective ion permeability, and they are widely distributed in mammals and single-cell yeast and serve as crucial mediators of sensory signals. However, the relevant information concerning TRP channels in Aspergillus nidulans remains inadequately understood. In this study, by gene deletion, green fluorescent protein tagging, and cytosolic Ca2+ transient monitoring techniques, the biological functions of three potential TRP channels (TrpA, TrpB, and TrpC) have been explored for which they play distinct and multiple roles in hyphal growth, conidiation, responsiveness to external stress, and regulation of intracellular Ca2+ homeostasis...

Orai1 is the pore-forming subunit of the Ca2+ -release activated Ca2+ channels that mediate store-operated Ca2+ entry (SOCE) in excitable and non-excitable cells. Two Orai1 forms have been identified in mammalian cells, the full-length variant Orai1α, and the short form Orai1β, lacking the N-terminal 63 amino acids. Stem cells were isolated from non-tumoral breast epithelial cells of the MCF10A cell line, and the most representative ER+ , HER2 or triple negative breast cancer cell lines MCF7, SKBR3 and MDA-MB-231, respectively...

Melanopsin signaling within ipRGC subtypes impacts a broad range of behaviors from circadian photoentrainment to conscious visual perception. Yet, how melanopsin phototransduction within M1-M6 ipRGC subtypes impacts cellular signaling to drive diverse behaviors is still largely unresolved. The identity of the phototransduction channels in each subtype is key to understanding this central question but has remained controversial. In this study, we resolve two opposing models of M4 phototransduction, demonstrating that hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are dispensable for this process and providing support for a pathway involving melanopsin-dependent potassium channel closure and canonical transient receptor potential (TRPC) channel opening...

Atrial fibrillation (AFIB) and ventricular fibrillation (VFIB) are two common cardiovascular diseases that cause numerous deaths worldwide. Medical staff usually adopt long-term ECGs as a tool to diagnose AFIB and VFIB. However, since ECG changes are occasionally subtle and similar, visual observation of ECG changes is challenging. To address this issue, we proposed a multi-angle dual-channel fusion network (MDF-Net) to automatically recognize AFIB and VFIB heartbeats in this work. MDF-Net can be seen as the fusion of a task-related component analysis (TRCA)-principal component analysis (PCA) network (TRPC-Net), a canonical correlation analysis (CCA)-PCA network (CPC-Net), and the linear support vector machine-weighted softmax with average (LS-WSA) method...

Calcium (Ca2+) plays a critical role in podocyte function. The Ca2+-sensitive receptors on the cell surface can sense changes in Ca2+ concentration, and Ca2+ flow into podocytes, after activation of Ca2+ channels (such as transient receptor potential canonical (TRPC) channels and N-type calcium channels) by different stimuli. In addition, the type 2 ryanodine receptor (RyR2) and the voltage-dependent anion channel 1 (VDAC1) on mitochondrial store-operated calcium channels (SOCs) on the endoplasmic reticulum maintain the Ca2+ homeostasis of the organelle...

Canonical TRP (TRPC) channels are a still enigmatic family of signaling molecules with multimodal sensing features. These channels enable Ca2+ influx through the plasma membrane to control a diverse range of cellular functions. Based on both regulatory- and recently uncovered structural features, TRPC channels are considered to coordinate Ca2+ and other divalent cations not only within the permeation path but also at additional sensory sites. Analysis of TRPC structures by cryo-EM identified multiple regulatory ion binding pockets...

Ion channels play a crucial role in a wide range of biological processes, including cell cycle regulation and cancer progression. In particular, the transient receptor potential (TRP) family of channels has emerged as a promising therapeutic target due to its involvement in several stages of cancer development and dissemination. TRP channels are expressed in a large variety of cells and tissues, and by increasing cation intracellular concentration, they monitor mechanical, thermal, and chemical stimuli under physiological and pathological conditions...

Transient receptor potential (TRP) ion channels have diverse activation mechanisms including physical stimuli, such as high or low temperatures, and a variety of intracellular signaling molecules. Regulation by phosphoinositides and their derivatives is their only known common regulatory feature. For most TRP channels, phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2 ] serves as a cofactor required for activity. Such dependence on PI(4,5)P2 has been demonstrated for members of the TRPM subfamily and for the epithelial TRPV5 and TRPV6 channels...

The transient receptor potential (TRP) channel superfamily is a group of non-selective cation channels functioning as cellular sensors for a wide range of physical, chemical and environmental stimuli. According to sequence homology, TRP channels are categorized into six subfamilies: TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPA (ankyrin), TRPML (mucolipin), and TRPP (polycystin). They are widely expressed in different cell types and tissues and have essential roles in various physiological and pathological processes by regulating the concentration of ions (Ca2+ , Mg2+ , Na+ and K+ ) and influencing intracellular signaling pathways...

BACKGROUND: Diabetes mellitus type 2 is a risk factor for developing heart failure and myocardial fibrosis, but there is no specific therapy for diabetic heart disease. 1-[2-(4-methoxyphenyl)]-2-[3-(4-methoxyphenyl) propoxy]ethyl-1H-imidazole (SKF96365) is regarded as an inhibitor of receptor-mediated calcium ion (Ca2+) entry. This study aimed to explore the effects of SKF96365 on diabetic myocardial fibrosis. METHODS: A type 2 diabetic rat model induced by a high-sugar and high-fat diet combined with streptozotocin was established...

Optically dark excitons determine a wide range of properties of photoexcited semiconductors yet are hard to access via conventional time-resolved spectroscopies. Here, we develop a time-resolved ultrafast photocurrent technique (trPC) to probe the formation dynamics of optically dark excitons. The nonlinear nature of the trPC makes it particularly sensitive to the formation of excitons occurring at the femtosecond time scale after the excitation. As a proof of principle, we extract the interlayer exciton formation time of 0...