Related Experiment Video
Updated: Apr 11, 2026
13:07
One-channel Cell-attached Patch-clamp Recording
Published on: June 9, 2014
25.7K
Flow-sensitive K + channels link flow to piezo1/PI3K/Akt1 pathway
Biorxiv : the Preprint Server for Biology
|April 10, 2026
Summary
Endothelial Kir2.1 is crucial for vascular function, linking the glycocalyx to flow signaling. Its loss impairs flow-induced vasodilation in hypertension and aging, but can be restored by Kir2.1 restoration.
Area of Science:
- Vascular biology
- Endothelial cell physiology
- Mechanotransduction
Background:
- Endothelial response to blood flow is vital for vascular health and disease.
- Endothelial Kir2.1 is known to be essential for flow-induced signaling and vasodilation.
- The precise integration of Kir2.1 with other flow-sensing pathways was not fully understood.
Purpose of the Study:
- To elucidate the mechanistic role of endothelial Kir2.1 in flow-induced signaling pathways.
- To investigate the integration of Kir2.1 with calcium influx channels (Piezo1, TRPV4) and the endothelial glycocalyx.
- To determine the physiological relevance of Kir2.1 in conditions like hypertension and aging.
Main Methods:
- Real-time electrophysiological recordings during flow exposure.
- Calcium (Ca 2+ ) imaging and pressure myography of resistance arteries.
- Echocardiography and genetic manipulation of endothelial channels.
Main Results:
- Kir2.1 is essential for flow-induced PI3K and Akt1/eNOS phosphorylation, with myristoylated Akt1 bypassing this requirement.
- Kir2.1 mediates flow-induced Ca 2+ influx via Piezo1 and TRPV4, but is not required for channel activation itself.
- Flow activation of Kir2.1 depends on Syndecan1, linking the glycocalyx to downstream signaling; Kir2.1 is suppressed by Angiotensin-II and aging, impairing flow-induced vasodilation (FIV).
Conclusions:
- Kir2.1 acts as a key molecular linker between the endothelial glycocalyx, Piezo1-mediated calcium influx, and downstream signaling in mechanotransduction.
- Loss of endothelial Kir2.1 function significantly contributes to impaired FIV in Angiotensin-II-induced hypertension and aging.
- Restoring endothelial Kir2.1 can fully recover FIV in these pathological conditions.
More Related Videos
07:17Electrophysiological Recordings of Single-cell Ion Currents Under Well-defined Shear Stress
Published on: August 2, 2019
6.7K
05:42Measurement of Ion Concentration in the Unstirred Boundary Layer with Open Patch-Clamp Pipette: Implications in Control of Ion Channels by Fluid Flow
Published on: January 7, 2019
6.8K
Related Concept Videos
01:12Mechanically-gated Ion Channels
8.1K
Mechanically-gated ion channels are proteins found in eukaryotic and prokaryotic cell membranes that open in response to mechanical stress. Tension, compression, swelling, and shear stress can alter the conformation of the protein, opening a transmembrane channel that allows the passage of ions for signal transmission. In eukaryotes, mechanically-gated channels are distributed in several regions like the neurons, lungs, skin, bladder, and heart, where they play critical roles in numerous...
8.1K
01:12Mechanically-gated Ion Channels
5.7K
5.7K
01:15Amplifying Signals via Second Messengers
9.6K
Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
9.6K
01:22PI3K/mTOR/AKT Signaling Pathway
6.4K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
6.4K
01:11IP3/DAG Signaling Pathway
16.0K
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
16.0K
01:19The Role of Ion Channels in Neuronal Computation
4.3K
A postsynaptic neuron usually receives numerous impulses from several other presynaptic neurons. The axon hillock of the postsynaptic neuron integrates all these signals and determines the likelihood of firing an action potential.
Sometimes a single EPSP is strong enough to induce an action potential in the postsynaptic neuron. However, multiple presynaptic inputs must often create EPSPs around the same time for the postsynaptic neuron to be sufficiently depolarized to fire an action potential....
Sometimes a single EPSP is strong enough to induce an action potential in the postsynaptic neuron. However, multiple presynaptic inputs must often create EPSPs around the same time for the postsynaptic neuron to be sufficiently depolarized to fire an action potential....
4.3K