Piezo1 in Smooth Muscle Cells Is Involved in Hypertension-Dependent Arterial Remodeling

Retailleau, Kevin; Duprat, Fabrice; Arhatte, Malika; Ranade, Sanjeev S.; Peyronnet, Rémi; Martins, Joana Raquel; Jodar, Martine; Moro, Céline; Offermanns, Stefan; Feng, Yuanyi; Demolombe, Sophie; Patel, Amanda; Honoré, Eric

doi:10.1016/j.celrep.2015.09.072

Cited by 263 publications

(260 citation statements)

References 55 publications

Supporting

Mentioning

251

Contrasting

Unclassified

Order By: Relevance

“…Based on the differences in sensitivity seen between bleb-attached and cell-attached Piezo1 channels, the authors proposed that the cytoskeleton has a mechano-protective effect on Piezo1, whereby presence of the cytoskeleton makes it harder to open the channel. These findings are consistent with reports by Retailleau et al wherein they found that knocking out filamin, a scaffold protein that connects the actin network to membrane proteins, made it easier to activate the channel in cell-attached patch clamp assays [43]. …”

Section: Effects Of the Cytoskeleton On Piezo1 Activationsupporting

confidence: 93%

How cells channel their stress: Interplay between Piezo1 and the cytoskeleton

Nourse

Pathak

2017

Seminars in Cell & Developmental Biology

171

160

View full text Add to dashboard Cite

Cells constantly encounter mechanical stimuli in their environment, such as dynamic forces and mechanical features of the extracellular matrix. These mechanical cues are transduced into biochemical signals, and integrated with genetic and chemical signals to modulate diverse physiological processes. Cells also actively generate forces to internally transport cargo, to explore the physical properties of their environment and to spatially position themselves and other cells during development. Mechanical forces are therefore central to development, homeostasis, and repair. Several molecular and biophysical strategies are utilized by cells for detecting and generating mechanical forces. Here we discuss an important class of molecules involved in sensing and transducing mechanical forces – mechanically-activated ion channels. We focus primarily on the Piezo1 ion channel, and examine its relationship with the cellular cytoskeleton.

show abstract

Section: Effects Of the Cytoskeleton On Piezo1 Activationsupporting

confidence: 93%

How cells channel their stress: Interplay between Piezo1 and the cytoskeleton

Nourse

Pathak

2017

Seminars in Cell & Developmental Biology

171

160

View full text Add to dashboard Cite

show abstract

“…Like K2P channels, Piezo has recently been reconstituted in different lipid based assays devoid of cytoskeletal intervention and shown to be directly gated by lipid tension [52, 53]. However channel gating is definitely modulated by cytoskeleton [53, 54]. These channels have become the focus of many studies into the gating mechanism of cationic MSCs and their physiological role in both specialized and non-specialized mechanosensors (for review see [55]).…”

Section: Piezo – the Missing Linkmentioning

confidence: 99%

Piezo channels and GsMTx4: Two milestones in our understanding of excitatory mechanosensitive channels and their role in pathology

Suchyna

2017

Progress in Biophysics and Molecular Biology

View full text Add to dashboard Cite

Discovery of Piezo channels and the reporting of their sensitivity to the inhibitor GsMTx4 were important milestones in the study of non-selective cationic mechanosensitive channels (MSCs) in normal physiology and pathogenesis. GsMTx4 had been used for years to investigate the functional role of cationic MSCs, especially in muscle tissue, but with little understanding of its target or inhibitory mechanism. The sensitivity of Piezo channels to bilayer stress and its robust mechanosensitivity when expressed in heterologous systems were keys to determining GsMTx4’s mechanism of action. However, questions remain regarding Piezo’s role in muscle function due to the non-selective nature of GsMTx4 inhibition toward membrane mechanoenzymes and the implication of MCS channel types by genetic knockdown. Evidence supporting Piezo like activity, at least in the developmental stages of muscle, is presented. While the MSC targets of GsMTx4 in muscle pathology are unclear, its muscle protective effects are clearly demonstrated in two recent in situ studies on normal cardiomyocytes and dystrophic skeletal muscle. The muscle protective function may be due to the combined effect of GsMTx4’s inhibitory action on cationic MSCs like Piezo and TRP, and its potentiation of repolarizing K+ selective MSCs like K2P and SAKCa. Paradoxically, the potent in vitro action of GsMTx4 on many physiological functions seems to conflict with its lack of in situ side-effects on normal animal physiology. Future investigations into cytoskeletal control of sarcolemma mechanics and the suspected inclusion of MSCs in membrane micro/nano sized domains with distinct mechanical properties will aide our understanding of this dichotomy.

show abstract

“…258 In addition Piezo1 can be inhibited by the cyctoskeleton-protein cross-linker filamin A in smooth muscle. 259 Thus, the cytoskeleton may, both, cause MGC activation or protect them from opening. An additional layer of complexity arises from the fact that cytoskeletal integrity affects membrane tension and shape of the cell and its organelles.…”

Section: Discussionmentioning

confidence: 99%

Cardiac Mechano-Gated Ion Channels and Arrhythmias

Peyronnet

Nerbonne

Kohl

2016

Circulation Research

Self Cite

175

167

View full text Add to dashboard Cite

Mechanical forces will have been omnipresent since the origin of life, and living organisms have evolved mechanisms to sense, interpret and respond to mechanical stimuli. The cardiovascular system in general, and the heart in particular, are exposed to constantly changing mechanical signals, including stretch, compression, bending, and shear. The heart adjusts its performance to the mechanical environment, modifying electrical, mechanical, metabolic, and structural properties over a range of time scales. Many of the underlying regulatory processes are encoded intra-cardially, and are thus maintained even in heart transplant recipients. Although mechano-sensitivity of heart rhythm has been described in the medical literature for over a century, its molecular mechanisms are incompletely understood. Thanks to modern biophysical and molecular technologies, the roles of mechanical forces in cardiac biology are being explored in more detail, and detailed mechanisms of mechano-transduction have started to emerge. Mechano-gated ion channels are cardiac mechano-receptors. They give rise to mechano-electric feedback, thought to contribute to normal function, disease development, and, potentially, therapeutic interventions. In this review, we focus on acute mechanical effects on cardiac electrophysiology, explore molecular candidates underlying observed responses, and discuss their pharmaceutical regulation. From this, we identify open research questions and highlight emerging technologies that may help in addressing them. Cardiac electrophysiology is acutely affected by the heart’s mechanical environment. Mechano-electric feedback affects excitability, conduction, and electrical load, and remains an underestimated player in arrhythmogenesis. The utility of therapeutic interventions targeting acute mechano-electrical transduction is an open field worthy of further study.

show abstract

Piezo1 in Smooth Muscle Cells Is Involved in Hypertension-Dependent Arterial Remodeling

Cited by 263 publications

References 55 publications

How cells channel their stress: Interplay between Piezo1 and the cytoskeleton

How cells channel their stress: Interplay between Piezo1 and the cytoskeleton

Piezo channels and GsMTx4: Two milestones in our understanding of excitatory mechanosensitive channels and their role in pathology

Cardiac Mechano-Gated Ion Channels and Arrhythmias

Contact Info

Product

Resources

About