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What physical force actually opens Piezo1?

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In HEK293t patches, Piezo1 opened to both convex and concave stretch but tracked lateral tension with T50 ≈ 1.4 mN/m; resting tension drove inactivation and thereby tuned apparent mechanical sensitivity.

Source

Mechanical sensitivity of Piezo1 ion channels can be tuned by cellular membrane tension

Lewis AH, Grandl J · eLife · 2015

doi.org/10.7554/elife.12088Read the full paper ↗362 citationscc by

Study at a glance

Design
Animal / in-vitro — Patch-clamp plus simultaneous imaging of membrane geometry in HEK293t cells expressing mouse Piezo1, across cell-attached, inside-out, and outside-out patches
N
N=15 · Primary P50: N=15 cell-attached negative-pressure Piezo1 patches (N=12 positive); additional inside-out/outside-out and pcDNA controls
Population
HEK293t cells transiently expressing mouse Piezo1-IRES-GFP (empty-vector controls)
Outcome
Whether curvature or lateral tension opens Piezo1; T50; effect of resting tension on inactivation/availability

Structured fields used in claim comparison tables when every cited study has a complete layer.

What they did

Recorded Piezo1 stretch currents at −80 mV in three patch configurations while imaging pipette membrane geometry, converted pressure to tension via Laplace’s law, and used flattening prepulses to remove resting curvature/tension before test steps.

What they found

Currents appeared from −5 mmHg in cell-attached patches (P50 −16.7 ± 2.8 mmHg, N=15) and also with positive pressure. Inside-out negative P50 was −35.8 ± 4.0 mmHg (N=10). Tension for half-activation was T50 = 1.4 ± 0.1 mN/m. Resting tension inactivated channels, so flattening prepulses increased available current.

The limits

What it doesn't show

Heterologous HEK patches cannot prove cytoskeleton is irrelevant in tissues, nor how Piezo1 senses tension at atomic scale; local curvature could still matter.

Key terms

Piezo1
Large mechanically activated cation channel; mammalian touch/vascular mechanosensor studied here in HEK cells.
Lateral membrane tension
In-plane force in the bilayer (mN/m); the stimulus that best explained Piezo1 opening.
T50
Tension for half-maximal activation; 1.4 ± 0.1 mN/m here—very sensitive vs many other MS channels.
Inactivation
Current decay during a sustained stimulus; resting tension can trap Piezo1 in unavailable states.
Laplace’s law
T = R·Δp/2 relating pipette pressure and imaged radius of curvature to tension.
P50
Pressure for half-maximal current; depended on patch configuration and pressure sign until converted to tension.

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Piezo1 T50 was about:

Common questions

T50 for Piezo1?

1.4 ± 0.1 mN/m.

Cell-attached negative P50?

−16.7 ± 2.8 mmHg (N=15).

Did both curvatures work?

Yes—convex and concave stretch both opened Piezo1.

Role of resting tension?

It can inactivate channels and retune sensitivity.

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