PE-22-28
PE-22-28 is a synthetic heptapeptide derived from the naturally occurring peptide spadin (also known as PE 12-28). Spadin itself is a secreted peptide fragment of the sortilin propeptide (also called neurotensin receptor-3 or NTSR3). PE-22-28 was developed as a shortened, optimized analog of spadin, retaining only the seven most active amino acids from the parent sequence. It functions as a potent and selective antagonist of the TREK-1 (TWIK-related potassium channel1) receptor, a two-pore domain potassium channel that has been identified as a major target in the study of depression, neurogenesis, and neuroprotection. Research interest in PE-22-28 emerged from the seminal discovery that mice lacking the TREK1 channel gene (TREK-1 knockout mice) exhibited resistance to depression-like behaviors in standardized behavioral tests. This finding prompted researchers led by Dr. Jean Mazella and colleagues at the Institute of Molecular and Cellular Pharmacology (IPMC) in France to develop pharmacological agents capable of selectively blocking TREK-1. Spadin was the first endogenous peptide identified with this capability. However, spadin had limitations in terms of in vivo stability and half-life, with its antidepressant activity disappearing approximately seven hours after acute intraperitoneal administration in mice. To address these shortcomings, researchers analyzed the degradation products of spadin in blood serum and identified that the seven-amino-acid fragment corresponding to residues 22 through 28 of the sortilin propeptide retained the strongest TREK-1 inhibitory activity. This fragment, designated PE-22-28, demonstrated a dramatically improved IC50 of 0.12 nM for TREK-1 inhibition compared to an IC50 of 40.0 nM for spadin—representing an approximately 333-fold improvement in potency. PE-22-28 also showed improved in vivo stability, enhanced antidepressant activity in behavioral models, and the ability to stimulate both neurogenesis and synaptogenesis in the hippocampus within just four days of administration. PE-22-28 is currently classified as a research peptide and has not been approved by the FDA or any other regulatory agency for human therapeutic use. All available data are derived from preclinical studies conducted in cell culture systems and animal models, primarily mice. No human clinical trials have been published to date. Despite this early-stage status, PE-22-28 has generated significant interest in the fields of neuropharmacology, nootropic research, and neuropsychiatric medicine due to its unique mechanism of action, rapid onset of effects, and favorable preclinical safety profile.
How It Works Mechanism of Action: TREK-1 Channel Inhibition
The primary mechanism of action of PE-22-28 centers on its role as a selective antagonist of the TREK-1 potassium channel. TREK-1 belongs to the two-pore domain potassium channel (K2P) family, which plays a critical role in setting the resting membrane potential of neurons and regulating their overall excitability. When TREK-1 channels are open and functioning normally, they allow potassium ions to flow out of the neuron, which hyperpolarizes the cell membrane and reduces the likelihood that the neuron will fire an action potential. PE-22-28 binds to and inhibits TREK-1 channels with high specificity. This inhibition reduces the outward flow of potassium ions, which in turn increases the excitability of the neuron and makes it more likely to depolarize and fire. In brain regions associated with mood regulation— such as the prefrontal cortex, amygdala, and hippocampus—this increased neuronal excitability translates into enhanced serotonergic neurotransmission. Specifically, PE-22-28 has been shown to increase the firing rate of serotonin (5-HT) neurons in the dorsal raphe nucleus, which is the primary origin of serotonergic projections to the forebrain. Importantly, PE-22-28 demonstrates high selectivity for TREK-1. Electrophysiological studies have confirmed that PE-22-28 does not significantly inhibit related K2P channels including TREK-2, TRAAK, TRESK, or TASK-1. It also shows no effect on the hERG (human ether-ago-go-related gene) cardiac potassium channel, which is a critical safety marker in drug development. This selectivity is believed to be a major factor in the peptide’s favorable side effect profile.
Downstream Signaling: Neurogenesis and Synaptogenesis
Beyond its direct effects on neuronal excitability, PE-22-28 triggers a cascade of downstream signaling events that promote structural and functional changes in the brain. Among the most significant of these is the upregulation of CREB (cAMP response element-binding protein), a transcription factor that plays a central role in neuronal plasticity, memory formation, and neuronal survival. CREB activation is considered a hallmark of effective antidepressant therapy, and its upregulation by PE-22-28 has been documented after just four days of treatment in mouse models. PE-22-28 also promotes hippocampal neurogenesis—the growth of new neurons in the hippocampus—as demonstrated by increased incorporation of BrdU (5-bromo-2’-deoxyuridine), an exogenous marker used to detect actively dividing cells. Studies have shown that PE-22-28 approximately doubles the number of BrdU-positive cells in the hippocampus compared to saline controls. Additionally, PE-22-28 promotes synaptogenesis, as evidenced by increased expression of PSD-95 (postsynaptic density protein 95), a key marker of synapse formation. These findings suggest that PE-22-28 not only alleviates depressive symptoms but may also address the underlying structural deficits in the hippocampus that are associated with depressive disorders.
Molecular Structure PE-22-28 Sequence: GVSWGLR Molecular Formula: C₃₅H₅₅N₁₁O₉ Molecular Weight: 773.89 g/mol CAS Number: 1801959-12-5 Parent Compound (Spadin): YAPLPRWSGPIGVSWGLR (PE 12-28), MW 2012.35 g/mol
Research Benefits Antidepressant Activity PE-22-28 has demonstrated potent antidepressant activity in multiple validated behavioral models of depression in mice, including the forced swimming test (FST), the novelty-suppressed feeding test (NSF), and the learned helplessness paradigm. In the forced swimming test, mice treated with PE-22-28 showed a statistically significant reduction in immobility time compared to saline-treated controls, with effects observed at doses as low as 3.0–4.0 µg/kg administered intraperitoneally. This represents a roughly 25-fold reduction in the effective dose compared to spadin (100 µg/kg). PE-22-28 also showed efficacy when administered by oral gavage at a dose of 1.0 mg/kg, suggesting potential for oral bioavailability through modified delivery systems. One of the most remarkable findings is the speed of onset. While traditional antidepressants such as SSRIs typically require two to six weeks of continuous administration before therapeutic effects become apparent, PE-22-28 demonstrated significant antidepressant activity after a subchronic treatment period of just four days. This rapid onset is comparable to or faster than ketamine, which is currently considered the benchmark for rapid-acting antidepressant therapy.
Neurogenesis and Brain Plasticity
The ability of PE-22-28 to stimulate hippocampal neurogenesis within just four days of treatment is one of its most scientifically significant properties. The hippocampus is one of only two brain regions where neurogenesis occurs in the adult brain, and its volume is consistently found to be reduced in patients with major depressive disorder and other affective disorders. Long-term treatment with conventional antidepressants is known to stimulate hippocampal neurogenesis, and this neurogenic effect is increasingly viewed as a necessary component of their therapeutic mechanism rather than merely a secondary consequence. PE-22-28 approximately doubles the number of newly proliferating cells in the hippocampus as measured by BrdU incorporation and simultaneously doubles the rate of synapse formation as
indicated by PSD-95 expression. The peptide also significantly upregulates CREB, which is a master regulator of genes involved in neuronal survival, synaptic plasticity, and memory formation. These combined effects suggest that PE-22-28 may be capable of reversing the hippocampal atrophy associated with chronic depression, potentially addressing the disease at its structural and physiological roots rather than merely masking symptoms.
Post-Stroke Depression
Post-stroke depression (PSD) is a common and debilitating complication following cerebral ischemia, affecting an estimated 30 to 50 percent of stroke survivors. PSD is particularly refractory to standard antidepressant treatment. Research has identified TREK-1 overexpression as a likely causative factor in the development of PSD. In experimental mouse models of cerebral ischemia, this upregulation of TREK-1 can be suppressed or reversed using TREK-1 blockers such as PE-22-28. Moreover, studies have demonstrated that TREK-1-deficient mice exhibit smaller infarction sizes, less blood-brain barrier breakdown, reduced immune cell invasion, and better neurological function following experimentally induced stroke. These findings suggest that PE-22-28 may have dual benefits in the post-stroke setting: both as an antidepressant and as a neuroprotective agent.
Cognitive Enhancement and Nootropic Potential
The hippocampus plays a central role not only in mood regulation but also in learning, memory consolidation, and spatial navigation. The ability of PE-22-28 to stimulate neurogenesis and synaptogenesis in this critical brain structure, combined with its upregulation of CREB—a transcription factor directly linked to long-term memory formation and spatial memory development—suggests significant nootropic potential. CREB activation has been a longstanding drug target for cognitive enhancement, and the ability of PE-22-28 to rapidly upregulate CREB positions it as a compound of interest in the study of learning, memory, and cognitive performance.
Neuroprotection and Neurodegenerative Disease
Research in Alzheimer’s disease models has revealed a downregulation of CREB, and scientists have long sought pharmacological agents capable of boosting CREB activity as a means of treating or preventing neurodegenerative conditions. PE-22-28, through its ability to upregulate CREB and stimulate neurogenesis, is being actively investigated for its potential to both prevent and reverse the symptoms of Alzheimer’s disease. Additionally, the neuroprotective properties of TREK-1 modulation—including protection against excitotoxicity and reduction of ischemic damage—position PE-22-28 as a candidate compound for research into a range of neurodegenerative and neurotraumatic conditions.
Seizure Resistance
One of the more surprising findings in PE-22-28 research involves its relationship to seizure activity. Complete knockout of the TREK-1 channel in mice is known to significantly increase seizure susceptibility and reduce the normal neuroprotective capacity of this potassium channel. There was initial concern that pharmacological blockade of TREK-1 by PE-22-28 would similarly increase seizure risk. However, research has demonstrated the opposite: mice treated with spadin and PE-22-28 not only showed no enhancement of seizure activity but were actually more resistant to developing generalized seizures compared to untreated controls. PE-22-28 appeared to provide even more profound protective effects than spadin in this regard, suggesting a nuanced pharmacological mechanism distinct from simple channel knockout.
Muscle Function
Emerging research suggests that TREK-1 also plays an important role in the response of muscle tissue to mechanical stimulation. TREK-1 blockade appears to increase contractility in muscle tissue, while activation of the channel promotes muscle relaxation. While this aspect of TREK-1 physiology is still in the early stages of investigation, there is hope that understanding the role of molecules like PE-22-28 in muscle contraction and relaxation may open new pathways for treating conditions such as myogenic bladder dysfunction and for understanding the broader physiology of muscle performance.
What the Science Shows Key Study: Shortened Spadin Analogs (Djillani et al., 2017) This foundational study, published in Frontiers in Pharmacology, describes the rational design and characterization of PE-22-28 and its analogs. Researchers first analyzed the degradation products of spadin in mouse serum and identified two shortened peptides. Through systematic screening using patch-clamp electrophysiology on hTREK-1/HEK cells, PE-22-28 was identified as the shortest and most potent TREK-1 inhibitor with an IC50 of 0.12 nM. The study demonstrated that PE-22-28 exhibited significant antidepressant activity in the FST, NSF, and learned helplessness tests at doses approximately 25-fold lower than spadin. Sub-chronic treatment (four days) increased hippocampal neurogenesis (BrdU-positive cells) and synaptogenesis (PSD-95 expression). Critically, PE-22-28 showed no inhibition of TREK-2, TRAAK, TRESK, TASK-1, or hERG channels, confirming its high selectivity for TREK-1.
Spadin as a Novel Antidepressant (Mazella et al., 2010)
Published in PLoS Biology, this was the landmark study that first identified spadin as an endogenous TREK-1 inhibitor with antidepressant properties. The study demonstrated that TREK-1 knockout mice are resistant to depression and that spadin treatment mimics this effect.
Importantly, spadin was shown to boost both neurogenesis and serotonergic neuron firing rates, establishing the mechanistic framework upon which PE-22-28 research would later build.
Absence of TREK-1-Related Side Effects (Moha Ou Maati et al., 2012) Published in Neuropharmacology, this study specifically addressed safety concerns regarding spadin and its analogs. Despite TREK-1’s known roles in pain sensitivity, seizure activity, and cardiac ischemia, the study found that spadin treatment produced none of the anticipated side effects. Spadin did not enhance pain sensitivity, did not increase seizure susceptibility, and did not affect cardiac function. These findings were critical in establishing the favorable safety profile that would later be confirmed for PE-22-28.
Regulation of Synaptogenesis (Devader et al., 2015)
Published in the British Journal of Pharmacology, this study provided detailed evidence that spadin and its analogs regulate synaptogenesis both in vitro and in vivo. The study demonstrated increased PSD-95 expression—a marker of postsynaptic density and synapse formation—in the hippocampus of treated animals, providing molecular evidence for the structural brain changes induced by TREK-1 inhibition.
Role of TREK-1 in Health and Disease (Djillani et al., 2019) Published in Frontiers in Pharmacology, this comprehensive review examined the role of TREK1 across multiple organ systems. It detailed TREK-1’s involvement in depression, post-stroke depression, neuroprotection, pain perception, anesthesia, and cardiac function. The review highlighted the overexpression of TREK-1 in post-stroke depression models and its suppression by both SSRIs and TREK-1 blockers, establishing the rationale for PE-22-28’s potential use in PSD.
Dosing Protocol Important Disclaimer PE-22-28 is a research peptide that has not been approved by the FDA or any other regulatory body for human use. No human clinical trials have been published. The following dosing information is compiled from preclinical research data and is presented for educational and informational purposes only. Any use of this peptide should be conducted under the supervision of a qualified healthcare professional in a research setting.
Preclinical Dosing (Animal Studies)
In the primary research studies, PE-22-28 was administered to mice via intraperitoneal (IP) injection at doses ranging from 3.0 to 4.0 µg/kg body weight. This represented an approximately 25-fold reduction in effective dose compared to the parent compound spadin, which required 100 µg/kg. The peptide was also tested via oral gavage at a dose of 1.0 mg/kg with retained efficacy in the forced swimming test. Sub-chronic treatment protocols in these studies consisted of oncedaily administration for four consecutive days.
Reconstitution Guidelines
PE-22-28 is typically supplied in lyophilized (freeze-dried) powder form. For reconstitution, bacteriostatic water is the standard diluent. The peptide should be reconstituted slowly by directing the stream of water along the inner wall of the vial rather than directly onto the powder cake, and the vial should be gently swirled—never shaken—to dissolve the contents.
For an 8 mg vial: Add 2.0 mL of bacteriostatic water to yield a concentration of 4.0 mg/mL.
For a 10 mg vial: Add 2.0 mL of bacteriostatic water to yield a concentration of 5.0 mg/mL, or add 3.0 mL for a concentration of approximately 3.33 mg/mL.
Route of Administration
Based on the available preclinical research and anecdotal protocols, PE-22-28 is most commonly administered via subcutaneous injection. There is also emerging interest in intranasal delivery, with some clinical observations suggesting potentially enhanced effects through this route. The subcutaneous injection sites commonly used include the abdomen, thighs, and upper arms, with systematic rotation recommended to minimize local tissue irritation.
Side Effects Preclinical Safety Profile One of the most notable features of PE-22-28 in preclinical research is its remarkably clean side effect profile. Despite initial concerns that TREK-1 inhibition would produce adverse effects related to the channel’s known roles in pain sensitivity, seizure threshold, and cardiac function, extensive testing in mouse models has revealed none of these anticipated problems.
What Research Has Not Observed
No enhancement of pain sensitivity or hyperalgesia
No increase in seizure susceptibility (paradoxically, increased seizure resistance was observed)
No adverse cardiac effects or hERG channel inhibition
No effects on TREK-2, TRAAK, TRESK, or TASK-1 channels
No sedation or motor impairment at therapeutic doses
No withdrawal syndrome or discontinuation effects
No effects on libido or sexual function (a common complaint with SSRIs)
Potential Considerations
While the preclinical data are encouraging, it is important to note that all available safety data are derived from animal studies. No human clinical trials have been conducted, and the long-term safety profile in humans remains entirely unknown. As with any compound that modulates central nervous system activity, individual responses may vary. Some anecdotal reports have noted that higher doses may produce lethargy or excessive sedation in some individuals, though this remains unverified in controlled studies.
Contraindications and Precautions
Due to the absence of human clinical trial data, formal contraindications for PE-22-28 have not been established. However, based on its known mechanism of action and pharmacological properties, the following precautions should be considered:
Individuals currently taking antidepressant medications (SSRIs, SNRIs, MAOIs, tricyclics) should exercise extreme caution due to potential synergistic effects on serotonergic neurotransmission and the theoretical risk of serotonin syndrome.
Individuals with a history of seizure disorders should consult with a qualified healthcare professional, despite the paradoxical seizure-protective effects observed in animal studies.
Individuals with cardiac conditions should be monitored, although PE-22-28 has shown no hERG channel effects in preclinical testing.
Pregnant or nursing women should avoid PE-22-28, as no reproductive toxicity data are available.
Individuals under 18 years of age should not use this peptide.
Anyone with a history of bipolar disorder or mania should exercise particular caution, as compounds that enhance neuronal excitability could theoretically precipitate manic episodes.
Comparison with Other Antidepressant Approaches
Parameter
PE-22-28
SSRIs
Ketamine
Spadin
Target
TREK-1
SERT
NMDA
TREK-1
Onset of Action
~4 days
2–6 weeks
Hours
~4 days
Neurogenesis
Yes (rapid)
Yes (slow)
Yes
Yes
Side Effects
Minimal
Significant
Significant
Minimal
Potency (IC50)
0.12 nM
N/A
N/A
40 nM
In Vivo Stability
Improved
Good
Short
~7 hours
FDA Approved
No
Yes
Yes
No
PE-22-28 occupies a unique position in the landscape of antidepressant research. It combines the rapid onset of action seen with ketamine (though not quite as fast) with the neurogenic properties of SSRIs, all while maintaining a side effect profile that appears substantially cleaner than either. Compared to its parent compound spadin, PE-22-28 offers approximately 333-fold greater potency at TREK-1, improved in vivo stability, and equivalent or superior efficacy at dramatically lower doses.
Success Tips for Researchers
Start with the lowest effective dose and titrate gradually. PE-22-28 is an extremely potent compound with an IC50 in the sub-nanomolar range, and conservative dosing is advisable.
Use fresh reconstituted peptide for each experimental cycle. Once reconstituted, PE-2228 should be used within 28 to 30 days and kept refrigerated at 2–8°C.
Protect from light at all stages. Peptides are susceptible to photodegradation, which can reduce potency and alter pharmacological activity.
Rotate injection sites systematically when using subcutaneous administration to minimize local tissue irritation and ensure consistent absorption.
Document dosing, timing, route of administration, and all observations meticulously to maintain protocol consistency and enable reproducibility.
Do not combine with serotonergic agents without careful consideration of potential pharmacological interactions.
Allow the reconstituted vial to reach room temperature before drawing doses, as cold peptide solutions may precipitate or deliver inconsistent concentrations.
Consider intranasal delivery as an alternative route of administration if subcutaneous injection is not preferred, though note that dosing equivalences between routes have not been established in clinical studies.
Storage and Handling Lyophilized (Unreconstituted) Peptide
Short-term storage (weeks to months): Refrigerate at 2–8°C (35.6–46.4°F). Lyophilized peptides are generally stable at room temperature for several weeks, but refrigeration is preferred.
Long-term storage (months to years): Store in a freezer at -20°C (-4°F) or ideally at 80°C (-112°F) for maximum stability.
Keep vials sealed, away from moisture, and protected from light at all times.
Reconstituted Peptide
Store at 2–8°C (35.6–46.4°F) immediately after reconstitution.
Use within 28 to 30 days for optimal potency. Bacteriostatic water sterility is generally guaranteed for 28 days after first puncture.
Do not freeze reconstituted peptide, as freeze-thaw cycles can degrade the peptide and reduce its biological activity.
Allow the vial to reach room temperature before opening to reduce condensation inside the vial.
Use a new sterile syringe for each draw to maintain sterility and prevent contamination.
Legal Status
PE-22-28 is not approved by the U.S. Food and Drug Administration (FDA) or any other national regulatory authority for human therapeutic use. It is classified as a research chemical and is sold exclusively for in vitro laboratory research purposes. Products containing PE-22-28 are not medicines or drugs, and bodily introduction of any kind into humans or animals is strictly prohibited outside of approved research protocols. In the United States, PE-22-28 is legal to purchase and possess for research purposes. However, it may not be marketed, sold, or promoted as a dietary supplement, food additive, drug, or medical device.
Frequently Asked Questions What is PE-22-28? PE-22-28 is a synthetic seven-amino-acid peptide (sequence: GVSWGLR) derived from spadin, a naturally occurring peptide fragment of the sortilin propeptide. It is a potent and selective inhibitor of the TREK-1 potassium channel with an IC50 of 0.12 nM, representing approximately 333-fold greater potency than its parent compound spadin. How does PE-22-28 differ from spadin? PE-22-28 is a shortened version of spadin, retaining only seven of spadin’s seventeen amino acids. Despite its smaller size, PE-22-28 demonstrates approximately 333-fold greater potency for TREK-1 inhibition, improved in vivo stability, enhanced antidepressant activity at lower doses (3.0–4.0 µg/kg versus 100 µg/kg for spadin), and equivalent or superior neurogenic properties. Is PE-22-28 FDA-approved? No. PE-22-28 has not been approved by the FDA or any other regulatory agency for human use. All available data are from preclinical studies in cell culture and animal models. No human clinical trials have been published. What are the primary research applications of PE-22-28? PE-22-28 is being investigated for its potential roles in antidepressant therapy, hippocampal neurogenesis, synaptogenesis, post-stroke depression, neuroprotection, cognitive enhancement, seizure resistance, and the study of TREK-1 channel physiology. Does PE-22-28 have side effects? In preclinical studies, PE-22-28 has demonstrated one of the smallest side effect profiles of any existing or experimental treatment for depression. It has not been shown to affect pain sensitivity, seizure threshold, cardiac function, or other K2P channels. However, no human safety data are available. How quickly does PE-22-28 take effect? In mouse models, PE-22-28 demonstrated significant antidepressant activity after a sub-chronic treatment period of four days. This is substantially faster than conventional SSRIs (two to six weeks) and comparable to the rapid onset seen with ketamine. Can PE-22-28 be taken orally?
In animal studies, PE-22-28 retained antidepressant activity when administered by oral gavage at a dose of 1.0 mg/kg, suggesting some degree of oral bioavailability. However, like most peptides, it likely has limited oral absorption in its native form and is more commonly administered via injection or intranasal delivery in research settings. Who developed PE-22-28? PE-22-28 was developed by a research team led by Dr. Jean Mazella and colleagues at the Institute of Molecular and Cellular Pharmacology (IPMC) in France, based on their earlier work identifying spadin as an endogenous TREK-1 inhibitor with antidepressant properties.
References
1. Mazella J, et al. Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug design. PLoS Biol. 2010;8(4):e1000355. doi: 10.1371/journal.pbio.1000355. 2. Djillani A, Pietri M, Moreno S, Heurteaux C, Mazella J, Borsotto M. Shortened Spadin Analogs Display Better TREK-1 Inhibition, In Vivo Stability and Antidepressant Activity. Front Pharmacol. 2017;8:643. doi: 10.3389/fphar.2017.00643. 3. Djillani A, Mazella J, Heurteaux C, Borsotto M. Role of TREK-1 in Health and Disease, Focus on the Central Nervous System. Front Pharmacol. 2019;10:379. doi: 10.3389/fphar.2019.00379. 4. Duman RS, Nakagawa S, Malberg J. Regulation of adult neurogenesis by antidepressant treatment. Neuropsychopharmacology. 2001;25(6):836–844. doi: 10.1016/S0893133X(01)00358-X. 5. Malberg JE, Schechter LE. Increasing hippocampal neurogenesis: a novel mechanism for antidepressant drugs. Curr Pharm Des. 2005;11(2):145–155. doi: 10.2174/1381612053382223. 6. Katalinic N, et al. Ketamine as a new treatment for depression: a review of its efficacy and adverse effects. Aust N Z J Psychiatry. 2013;47(8):710–727. doi: 10.1177/0004867413486842. 7. Moha Ou Maati H, et al. Spadin as a new antidepressant: absence of TREK-1-related side effects. Neuropharmacology. 2012;62(1):278–288. doi: 10.1016/j.neuropharm.2011.07.019. 8. Devader C, et al. In vitro and in vivo regulation of synaptogenesis by the novel antidepressant spadin. Br J Pharmacol. 2015;172(10):2604–2617. doi: 10.1111/bph.13083. 9. Silva AJ, Kogan JH, Frankland PW, Kida S. CREB and memory. Annu Rev Neurosci. 1998;21:127–148. doi: 10.1146/annurev.neuro.21.1.127.
10. The Company of Biologists Limited. Mental health: spadin, a fast-acting antidepressant. Dis Model Mech. 2010;3(7–8):398. 11. Lei Q, et al. Response of the human detrusor to stretch is regulated by TREK-1, a two-poredomain (K2P) mechano-gated potassium channel. J Physiol. 2014;592(14):3013–3030. doi: 10.1113/jphysiol.2014.271718.