scholarly journals Novel Mechanistic Insights and Potential Therapeutic Impact of TRPC6 in Neurovascular Coupling and Ischemic Stroke

2021 ◽  
Author(s):  
Shashank Shekhar ◽  
Yedan Liu ◽  
Shaoxun Wang ◽  
Huawei Zhang ◽  
Xing Fang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Transient Receptor Potential ◽  
Glutamate Release ◽  
Neurovascular Coupling ◽  
Receptor Potential ◽  
Camp Response Element Binding ◽  
Element Binding Protein ◽  
Excitotoxic Damage ◽  
Transient Receptor ◽  
The Brain

Ischemic stroke is one of the most disabling diseases and a leading cause of death globally. Despite advances in medical care, the global burden of stroke continues to grow, as no effective treatments to limit or reverse ischemic injury to the brain are available. However, recent preclinical findings have revealed the potential role of transient receptor potential cation 6 (TRPC6) channels as endogenous protectors of neuronal tissue. Activating TRPC6 in various cerebral ischemia models has been found to prevent neuronal death, whereas blocking TRPC6 enhances sensitivity to ischemia. Evidence has shown that Ca2+ influx through TRPC6 activates cAMP response element-binding protein (CREB), an important transcription factor linked to neuronal survival. Additionally, TRPC6 activation may counter excitotoxic damage resulting from glutamate release by attenuating the activity of NMDA receptors of neurons by posttranslational means. Unresolved though, are the roles of TRPC6 channels in non-neuronal cells such as astrocytes and endothelial cells. Moreover, TRPC6 channels may have detrimental effects on the blood-brain barrier, although their exact role in neurovascular coupling requires further investigation. This review discusses evidence-based cell-specific aspects of TRPC6 in the brain to assess the potential targets for ischemic stroke management.

scholarly journals Novel Mechanistic Insights and Potential Therapeutic Impact of TRPC6 in Neurovascular Coupling and Ischemic Stroke

2021 ◽  
Vol 22 (4) ◽  
pp. 2074
Author(s):  
Shashank Shekhar ◽  
Yedan Liu ◽  
Shaoxun Wang ◽  
Huawei Zhang ◽  
Xing Fang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Transient Receptor Potential ◽  
Glutamate Release ◽  
Neurovascular Coupling ◽  
Receptor Potential ◽  
Element Binding Protein ◽  
Excitotoxic Damage ◽  
Transient Receptor ◽  
The Brain

Ischemic stroke is one of the most disabling diseases and a leading cause of death globally. Despite advances in medical care, the global burden of stroke continues to grow, as no effective treatments to limit or reverse ischemic injury to the brain are available. However, recent preclinical findings have revealed the potential role of transient receptor potential cation 6 (TRPC6) channels as endogenous protectors of neuronal tissue. Activating TRPC6 in various cerebral ischemia models has been found to prevent neuronal death, whereas blocking TRPC6 enhances sensitivity to ischemia. Evidence has shown that Ca2+ influx through TRPC6 activates the cAMP (adenosine 3’,5’-cyclic monophosphate) response element-binding protein (CREB), an important transcription factor linked to neuronal survival. Additionally, TRPC6 activation may counter excitotoxic damage resulting from glutamate release by attenuating the activity of N-methyl-d-aspartate (NMDA) receptors of neurons by posttranslational means. Unresolved though, are the roles of TRPC6 channels in non-neuronal cells, such as astrocytes and endothelial cells. Moreover, TRPC6 channels may have detrimental effects on the blood–brain barrier, although their exact role in neurovascular coupling requires further investigation. This review discusses evidence-based cell-specific aspects of TRPC6 in the brain to assess the potential targets for ischemic stroke management.

scholarly journals Calcium controls smooth muscle TRPC gene transcription via the CaMK/calcineurin-dependent pathways

2007 ◽  
Vol 292 (1) ◽  
pp. C553-C563 ◽  
Author(s):  
Sara Morales ◽  
Amalia Diez ◽  
Antonio Puyet ◽  
Pedro J. Camello ◽  
Cristina Camello-Almaraz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Protein Expression ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Camp Response Element Binding ◽  
Gene And Protein Expression ◽  
Element Binding Protein ◽  
Transient Receptor ◽  
Trpc Gene

Transient receptor potential protein family C (TRPC) has been proposed as a candidate for channels involved in capacitative Ca2+ entry (CCE) mechanisms, but the modulation of their gene expression remains unexplored. In this study we show that guinea pig gallbladder smooth muscle contains mRNA encoding TRPC1, TRPC2, TRPC3, and TRPC4 proteins whose abundance depends on cytosolic Ca2+ level ([Ca2+]i). Thus lowering the levels of cellular calcium with the chelators EGTA and BAPTA AM results in a downregulation of TRPC1–TRPC4 gene and protein expression. In contrast, activation of Ca2+ influx through L-type Ca2+ channels and Ca2+ release from intracellular stores induced an increase in TRPC1–TRPC4 mRNA and protein abundance. Activation of Ca2+/calmodulin-dependent kinases (CaMK) and phosphorylation of cAMP-response element binding protein accounts for the increase in TRPC mRNA transcription in response to L-type channel-mediated Ca2+ influx . In addition to this mechanism, activation of TRPC gene expression by intracellular Ca2+ release also involves calcineurin pathway. According to the proposed role for these channels, activation of CCE induced an increase in TRPC1 and TRPC3 mRNA abundance, which depends on the integrity of the calcineurin and CaMK pathways. These findings show for the first time an essential autoregulatory role of Ca2+ in Ca2+ homeostasis at the level of TRPC gene and protein expression.

scholarly journals Transient Receptor Potential Vanilloid in the Brain Gliovascular Unit: Prospective Targets in Therapy

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 334
Author(s):  
Huilong Luo ◽  
Xavier Declèves ◽  
Salvatore Cisternino
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Brain Diseases ◽  
Transient Receptor Potential Vanilloid ◽  
Main Role ◽  
Trpv Channels ◽  
Gliovascular Unit ◽  
Transient Receptor ◽  
The Brain

The gliovascular unit (GVU) is composed of the brain microvascular endothelial cells forming blood–brain barrier and the neighboring surrounding “mural” cells (e.g., pericytes) and astrocytes. Modulation of the GVU/BBB features could be observed in a variety of vascular, immunologic, neuro-psychiatric diseases, and cancers, which can disrupt the brain homeostasis. Ca2+ dynamics have been regarded as a major factor in determining BBB/GVU properties, and previous studies have demonstrated the role of transient receptor potential vanilloid (TRPV) channels in modulating Ca2+ and BBB/GVU properties. The physiological role of thermosensitive TRPV channels in the BBB/GVU, as well as their possible therapeutic potential as targets in treating brain diseases via preserving the BBB are reviewed. TRPV2 and TRPV4 are the most abundant isoforms in the human BBB, and TRPV2 was evidenced to play a main role in regulating human BBB integrity. Interspecies differences in TRPV2 and TRPV4 BBB expression complicate further preclinical validation. More studies are still needed to better establish the physiopathological TRPV roles such as in astrocytes, vascular smooth muscle cells, and pericytes. The effect of the chronic TRPV modulation should also deserve further studies to evaluate their benefit and innocuity in vivo.

scholarly journals The Role of Transient Receptor Potential (TRP) Channels in the Transduction of Dental Pain

2019 ◽  
Vol 20 (3) ◽  
pp. 526 ◽  
Author(s):  
Mohammad Hossain ◽  
Marina Bakri ◽  
Farhana Yahya ◽  
Hiroshi Ando ◽  
Shumpei Unno ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Glutamate Release ◽  
Receptor Potential ◽  
Functional Expression ◽  
Dental Pain ◽  
Post Translational Modifications ◽  
Transient Receptor ◽  
External Stimuli

Dental pain is a common health problem that negatively impacts the activities of daily living. Dentine hypersensitivity and pulpitis-associated pain are among the most common types of dental pain. Patients with these conditions feel pain upon exposure of the affected tooth to various external stimuli. However, the molecular mechanisms underlying dental pain, especially the transduction of external stimuli to electrical signals in the nerve, remain unclear. Numerous ion channels and receptors localized in the dental primary afferent neurons (DPAs) and odontoblasts have been implicated in the transduction of dental pain, and functional expression of various polymodal transient receptor potential (TRP) channels has been detected in DPAs and odontoblasts. External stimuli-induced dentinal tubular fluid movement can activate TRP channels on DPAs and odontoblasts. The odontoblasts can in turn activate the DPAs by paracrine signaling through ATP and glutamate release. In pulpitis, inflammatory mediators may sensitize the DPAs. They could also induce post-translational modifications of TRP channels, increase trafficking of these channels to nerve terminals, and increase the sensitivity of these channels to stimuli. Additionally, in caries-induced pulpitis, bacterial products can directly activate TRP channels on DPAs. In this review, we provide an overview of the TRP channels expressed in the various tooth structures, and we discuss their involvement in the development of dental pain.

scholarly journals Transient receptor potential melastatin 2 governs stress-induced depressive-like behaviors

2019 ◽  
Vol 116 (5) ◽  
pp. 1770-1775 ◽  
Author(s):  
Seung Yeon Ko ◽  
Sung Eun Wang ◽  
Han Kyu Lee ◽  
Sungsin Jo ◽  
Jinil Han ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Synaptic Function ◽  
Tissue Samples ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor ◽  
The Brain ◽  
Synapsin 1

Major depressive disorder (MDD) is a devastating disease that arises in a background of environmental risk factors, such as chronic stress, that produce reactive oxygen species (ROS) in the brain. The chronic stress-induced ROS production involves Ca2+ signals; however, the mechanism is poorly understood. Transient receptor potential melastatin type 2 (TRPM2) is a Ca2+-permeable cation channel that is highly expressed in the brain. Here we show that in animal models of chronic unpredictable stress (CUS), deletion of TRPM2 (Trpm2−/−) produces antidepressant-like behaviors in mice. This phenotype correlates with reduced ROS, ROS-induced calpain activation, and enhanced phosphorylation of two Cdk5 targets including synapsin 1 and histone deacetylase 5 that are linked to synaptic function and gene expression, respectively. Moreover, TRPM2 mRNA expression is increased in hippocampal tissue samples from patients with MDD. Our findings suggest that TRPM2 is a key agent in stress-induced depression and a possible target for treating depression.

scholarly journals The antipyretic effect of paracetamol occurs independent of transient receptor potential ankyrin 1‐mediated hypothermia and is associated with prostaglandin inhibition in the brain

2018 ◽  
Vol 32 (10) ◽  
pp. 5751-5759 ◽  
Author(s):  
Elahe Mirrasekhian ◽  
Johan L. Å. Nilsson ◽  
Kiseko Shionoya ◽  
Anders Blomgren ◽  
Peter M. Zygmunt ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Antipyretic Effect ◽  
Transient Receptor ◽  
The Brain

Protecting Oligodendrocytes by Targeting Non-Glutamate Receptors as a New Therapeutic Strategy for Ischemic Stroke

Pharmacology ◽  
2017 ◽  
Vol 100 (3-4) ◽  
pp. 148-152
Author(s):  
Pan Luo ◽  
Dong Liu ◽  
Lianjun Guo
Keyword(s):  
Ischemic Stroke ◽  
Glutamate Receptors ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Cellular Level ◽  
Transient Receptor Potential Channels ◽  
Excitatory Neurotransmitter ◽  
Cellular Targets ◽  
Potential Channels ◽  
The Brain

Ischemic stroke has many devastating effects within the brain. At the cellular level, excitotoxicity has been a popular pharmacological target for therapeutics. To date, many clinical trials have been performed with drugs that target excitatory neurotransmitter receptors, such as NMDA receptor agonists. The results, however, have been lackluster. Most efforts to understand the impacts of excitotoxicity on the brain have focused primarily on neurons, and to a lesser degree, on gliocytes as cellular targets. Recent evidence suggests that oligodendrocytes (OLGs), the myelin-forming cells in the central nervous system, are damaged by ischemia in a manner completely different from that in neurons. Whereas ischemia primarily damages neurons through overactivation of ionotropic glutamate receptors, the ischemia damage in OLGs occurs through overactivation of H+-gated transient receptor potential channels. Given the differential mechanisms of ischemic injury between neurons and OLGs, strategies to target non-glutamate receptors to prevent OLG damage/demyelination deserve greater attention in drug development. Such strategies, combined with neuroprotective measures, could provide an excellent therapeutic avenue for the treatment of ischemic stroke.

Sign in / Sign up

Export Citation Format

Share Document