Piezo channels | Ion channels | IUPHAR/BPS Guide to IMMUNOPHARMACOLOGY

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Piezo channels C

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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PIEZO proteins are the pore-forming subunits of trimeric ion channels that open rapidly in response to mechanical stimuli such as membrane stretch, allowing positively charged ions such as the calcium ion to flow into the cell to change cellular structure and function. The proteins are eukaryotic, not prokaryotic, and lack sequence or structural homology to other proteins. There are two main types: In humans, there is PIEZO1 of 2521 amino acids and PIEZO2 of 2752 amino acids, which can form homomeric PIEZO1 and PIEZO2 channels. Membrane stretching causes complex changes in the channels that include a reduced inward curvature, an expansion of the N-terminal transmembrane helical units and an opening of the central ion pore region comprising the last two C-terminal helices. When there is sustained membrane stretching, the channels may adapt by inactivating at various rates depending on the cell type and context. There are many roles of the channels in diverse organ systems including cardiovascular, gastrointestinal, haematological, hepatobiliary, immune, integumental, musculoskeletal, neuronal, reproductive, respiratory and urinary systems as well as adipose tissue and cancers. The expression and functions of PIEZO1 are broad and diverse across many cell types and organs, whereas PIEZO2 is more restricted.

Channels and Subunits

Targets of relevance to immunopharmacology are highlighted in blue

Piezo1 C Show summary »« Hide summary More detailed page go icon to follow link

Target Id

2945

Nomenclature

Piezo1

Previous and unofficial names

Genes

PIEZO1 (Hs), Piezo1 (Mm), Piezo1 (Rn)

Ensembl ID

ENSG00000103335 (Hs), ENSMUSG00000014444 (Mm), ENSRNOG00000056786 (Rn)

UniProtKB AC

Q92508 (Hs), E2JF22 (Mm), Q0KL00 (Rn)

Endogenous modulators

Cholesterol, 7-ketocholesterol, phosphatidylserine, phosphatidylinositol 4,5-bisphosphate, ceramide, docosahexaenoic acid, eicosapentaenoic acid, margaric acid, protons, amyloid beta (1-40) peptide

Physical activators

Membrane stretch, cell indentation, fluid shear stress, cell traction force, substrate stiffening

Selective activators

Yoda2b pEC₅₀ 6.9 [7] - Mouse

Yoda2 pEC₅₀ 6.8 [9]

Yaddle1 pEC₅₀ 6.4 [5]

Yoda1 pEC₅₀ 4.6 [10]

Jedi2 pEC₅₀ 3.8 [12] - Mouse

Jedi1 pEC₅₀ 3.8 [12] - Mouse

Inhibitors

salvianolic acid B pIC₅₀ 5.9 [8]

Dooku1 pIC₅₀ 5.9 [4], 5.8 [4]

escin pIC₅₀ 5.8 [13]

GsMTx-4 pIC₅₀ 5.4 [2]

benzbromarone pIC₅₀ 5.4 [6]

Gd³⁺ (@ 30 μM) [3]

ruthenium red (@ 30 μM) [3]

propofol (@ 50 μM) [15]

Functional characteristics

Activation and deactivation, a few milliseconds; Inactivation, time constant 15 ms at -80 mV ranging to seconds or minutes and slower at positive voltages; Unitary conductance, 29 pS; Ion selectivity, monovalent and divalent cations (PCa/PCs 1.21) - Mouse (Mm).

Comment

No small molecule or toxin binding sites are confirmed on the channel, although an interaction site for Yoda1 has been suggested. The evidence for selective activation is greatest for Yoda1 [4,11], but none of the activators is guaranteed to be selective and the selectivity achieved will likely depend on the concentration of the activator and the biological context in which it is administered. Yoda1 has low aqueous solubility, which may be a factor behind the range of pEC₅₀s observed for it [9]. Analogues such as Yoda2 have better aqueous solubility. Yoda1, Yoda2, Yoda2b, Yaddle1 and Dooku1 are chemically related molecules (Yoda1 analogues). OB-1 is thought to inhibit the channels via stomatin like 3 (STOML3; Q8TAV4), with its effect taking up to 3 hours to occur [14].

Piezo2 C Show summary »« Hide summary More detailed page go icon to follow link

Target Id

2946

Nomenclature

Piezo2

Previous and unofficial names

FAM38B | FAM38B2 | PIEZ2 | C18orf30

Genes

PIEZO2 (Hs), Piezo2 (Mm), Piezo2 (Rn)

Ensembl ID

ENSG00000154864 (Hs), ENSMUSG00000041482 (Mm), ENSRNOG00000038784 (Rn)

UniProtKB AC

Q9H5I5 (Hs), Q8CD54 (Mm)

Endogenous modulators

Phosphatidic acid, palmitoyl lysophosphatidic acid

Physical activators

Cell indentation

Inhibitors

GsMTx-4 pIC₅₀ 5.3 [1]

Gd³⁺ (@ 30μM) [3]

ruthenium red (@ 30 μM) [3]

propofol (@ 50 μM) [15]

Functional characteristics

Activation and deactivation, a few milliseconds; Inactivation, time constant 7 ms at -80 mV and slower at positive voltages; Unitary conductance, 24 pS; Ion selectivity, monovalent and divalent cations (PCa/PCs 1.34) - Mouse (Mm).

Comment

No small molecule or toxin binding sites are confirmed on the channel.

References

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1. Alcaino C, Knutson K, Gottlieb PA, Farrugia G, Beyder A. (2017) Mechanosensitive ion channel Piezo2 is inhibited by D-GsMTx4. Channels (Austin), 11 (3): 245-253. [PMID:28085630]

2. Bae C, Sachs F, Gottlieb PA. (2011) The mechanosensitive ion channel Piezo1 is inhibited by the peptide GsMTx4. Biochemistry, 50 (29): 6295-300. [PMID:21696149]

3. Coste B, Mathur J, Schmidt M, Earley TJ, Ranade S, Petrus MJ, Dubin AE, Patapoutian A. (2010) Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science, 330 (6000): 55-60. [PMID:20813920]

4. Evans EL, Cuthbertson K, Endesh N, Rode B, Blythe NM, Hyman AJ, Hall SJ, Gaunt HJ, Ludlow MJ, Foster R et al.. (2018) Yoda1 analogue (Dooku1) which antagonizes Yoda1-evoked activation of Piezo1 and aortic relaxation. Br J Pharmacol, 175 (10): 1744-1759. [PMID:29498036]

5. Goon S, Shiu Chen Liu C, Ghosh Dastidar U, Paul B, Mukherjee S, Sarkar HS, Desai M, Jana R, Pal S, Sreedevi NV et al.. (2024) Exploring the Structural Attributes of Yoda1 for the Development of New-Generation Piezo1 Agonist Yaddle1 as a Vaccine Adjuvant Targeting Optimal T Cell Activation. J Med Chem, 67 (10): 8225-8246. [PMID:38716967]

6. Liang P, Zhang Y, Wan YCS, Ma S, Dong P, Lowry AJ, Francis SJ, Khandelwal S, Delahunty M, Telen MJ et al.. (2024) Deciphering and disrupting PIEZO1-TMEM16F interplay in hereditary xerocytosis. Blood, 143 (4): 357-369. [PMID:38033286]

7. Ludlow MJ, Povstyan OV, Linley DM, Martin-Almedina S, Revill C, Cuthbertson K, Smith KA, Fay E, Fotiou E, Bush A et al.. (2025) PIEZO1 mechanical insensitivity in generalized lymphatic dysplasia with the potential for pharmacological rescue. iScience, Epun ahead of print. DOI: 10.1016/j.isci.2025.113110

8. Pan X, Wan R, Wang Y, Liu S, He Y, Deng B, Luo S, Chen Y, Wen L, Hong T et al.. (2022) Inhibition of chemically and mechanically activated Piezo1 channels as a mechanism for ameliorating atherosclerosis with salvianolic acid B. Br J Pharmacol, 179 (14): 3778-3814. [PMID:35194776]

9. Parsonage G, Cuthbertson K, Endesh N, Murciano N, Hyman AJ, Revill CH, Povstyan OV, Chuntharpursat-Bon E, Debant M, Ludlow MJ et al.. (2023) Improved PIEZO1 agonism through 4-benzoic acid modification of Yoda1. Br J Pharmacol, 180 (16): 2039-2063. [PMID:36457143]

10. Syeda R, Xu J, Dubin AE, Coste B, Mathur J, Huynh T, Matzen J, Lao J, Tully DC, Engels IH et al.. (2015) Chemical activation of the mechanotransduction channel Piezo1. Elife, 4. [PMID:26001275]

11. Wang S, Chennupati R, Kaur H, Iring A, Wettschureck N, Offermanns S. (2016) Endothelial cation channel PIEZO1 controls blood pressure by mediating flow-induced ATP release. J Clin Invest, 126 (12): 4527-4536. [PMID:27797339]

12. Wang Y, Chi S, Guo H, Li G, Wang L, Zhao Q, Rao Y, Zu L, He W, Xiao B. (2018) A lever-like transduction pathway for long-distance chemical- and mechano-gating of the mechanosensitive Piezo1 channel. Nat Commun, 9 (1): 1300. [PMID:29610524]

13. Wang Y, Chu T, Pan X, Bian Y, Li J. (2023) Escin ameliorates inflammation via inhibiting mechanical stretch and chemically induced Piezo1 activation in vascular endothelial cells. Eur J Pharmacol, 956: 175951. [PMID:37541373]

14. Wetzel C, Pifferi S, Picci C, Gök C, Hoffmann D, Bali KK, Lampe A, Lapatsina L, Fleischer R, Smith ES et al.. (2017) Small-molecule inhibition of STOML3 oligomerization reverses pathological mechanical hypersensitivity. Nat Neurosci, 20 (2): 209-218. [PMID:27941788]

15. Yu D, Bae C. (2025) Propofol inhibits Piezo mechanosensitive channels. Biophys J, [Epub ahead of print]. [PMID:40485107]

NC-IUPHAR subcommittee and family contributors

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Citation information

Database page citation:

David J. Beech. Piezo channels. Accessed on 12/09/2025. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=967.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Mathie AA, Peters JA, Veale EL, Striessnig J, Kelly E, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Ion channels. Br J Pharmacol. 180 Suppl 2:S145-S222.