Function (Oxford, England)最新文献

{"title":"Urine-based Detection of Congenital Portosystemic Shunt in C57BL/6 Mice.","authors":"Beng San Yeoh,&nbsp;Rachel M Golonka,&nbsp;Piu Saha,&nbsp;Mrunmayee R Kandalgaonkar,&nbsp;Yuan Tian,&nbsp;Islam Osman,&nbsp;Andrew D Patterson,&nbsp;Andrew T Gewirtz,&nbsp;Bina Joe,&nbsp;Matam Vijay-Kumar","doi":"10.1093/function/zqad040","DOIUrl":"https://doi.org/10.1093/function/zqad040","url":null,"abstract":"<p><p>Sporadic occurrence of congenital portosystemic shunt (PSS) at a rate of ∼1 out of 10 among C57BL/6 J mice, which are widely used in biomedical research, results in aberrancies in serologic, metabolic, and physiologic parameters. Therefore, mice with PSS should be identified as outliers in research. Accordingly, we sought methods to, reliably and efficiently, identify PSS mice. Serum total bile acids ≥ 40 µm is a <i>bona fide</i> biomarker of PSS in mice but utility of this biomarker is limited by its cost and invasiveness, particularly if large numbers of mice are to be screened. This led us to investigate if assay of urine might serve as a simple, inexpensive, noninvasive means of PSS diagnosis. Metabolome profiling uncovered that Krebs cycle intermediates, that is, citrate, α-ketoglutarate, and fumarate, were strikingly and distinctly elevated in the urine of PSS mice. We leveraged the iron-chelating and pH-lowering properties of such metabolites as the basis for 3 urine-based PSS screening tests: urinary iron-chelation assay, pH strip test, and phenol red assay. Our findings demonstrate the feasibility of using these colorimetric assays, whereby their readout can be assessed by direct observation, to diagnose PSS in an inexpensive, rapid, and noninvasive manner. Application of our urinary PSS screening protocols can aid biomedical research by enabling stratification of PSS mice, which, at present, likely confound numerous ongoing studies.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d4/cc/zqad040.PMC10413929.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10062481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lymphatic contractile dysfunction in mouse models of Cantú Syndrome with K_ATP channel gain-of-function.","authors":"Michael J Davis,&nbsp;Jorge A Castorena-Gonzalez,&nbsp;Hae Jin Kim,&nbsp;Min Li,&nbsp;Maria Remedi,&nbsp;Colin G Nichols","doi":"10.1093/function/zqad017","DOIUrl":"https://doi.org/10.1093/function/zqad017","url":null,"abstract":"<p><p>Cantú Syndrome (CS) is an autosomal dominant disorder caused by gain-of-function (GoF) mutations in the Kir6.1 and SUR2 subunits of K_ATP channels. K_ATP overactivity results in a chronic reduction in arterial tone and hypotension, leading to other systemic cardiovascular complications. However, the underlying mechanism of lymphedema, developed by >50% of CS patients, is unknown. We investigated whether lymphatic contractile dysfunction occurs in mice expressing CS mutations in Kir6.1 (Kir6.1[V65M]) or SUR2 (SUR2[A478V], SUR2[R1154Q]). Pressure myograph tests of contractile function of popliteal lymphatic vessels over the physiological pressure range revealed significantly impaired contractile strength and reduced frequency of spontaneous contractions at all pressures in heterozygous Kir6.1[V65M] vessels, compared to control littermates. Contractile dysfunction of intact popliteal lymphatics in vivo was confirmed using near-infrared fluorescence microscopy. Homozygous SUR2[A478V] vessels exhibited profound contractile dysfunction ex vivo, but heterozygous SUR2[A478V] vessels showed essentially normal contractile function. However, further investigation of vessels from all three GoF mouse strains revealed significant disruption in contraction wave entrainment, decreased conduction speed and distance, multiple pacemaker sites, and reversing wave direction. Tests of 2-valve lymphatic vessels forced to pump against an adverse pressure gradient revealed that all CS-associated genotypes were essentially incapable of pumping under an imposed outflow load. Our results show that varying degrees of lymphatic contractile dysfunction occur in proportion to the degree of molecular GoF in Kir6.1 or SUR2. This is the first example of lymphatic contractile dysfunction caused by a smooth muscle ion channel mutation and potentially explains the susceptibility of CS patients to lymphedema.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10194823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10057746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serendipity in senescence.","authors":"R A North","doi":"10.1093/function/zqac064","DOIUrl":"https://doi.org/10.1093/function/zqac064","url":null,"abstract":"","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/86/66/zqac064.PMC9809900.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10494832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overactive ATP-Sensitive K⁺ Channels Compromise Lymphatic Contractile Function in Cantú Syndrome.","authors":"Qadeer Aziz","doi":"10.1093/function/zqad030","DOIUrl":"https://doi.org/10.1093/function/zqad030","url":null,"abstract":"he lymphatic system is an extensive network of vessels that uns in parallel to the blood vasculature. Both networks play cruial roles in nourishing and protecting the body. Alongside its ole in “draina ge,” the l ymphatic system is also associated with ultisystem functions and disorders, including metabolic disrders, obesity, neurological disorders, and cardiac growth and e pair. Hence, a better understanding of its structural and funcional physiology and pathophysiology could help in the develpment of future therapeutics for not only traditional lymphatic isorders such as primary and secondary lymphedema but also n the potential treatment of organ-specific functions. Lymphatic vessels, like blood vessels, are composed of a ayer of endothelial cells surrounded by a thin layer of smooth uscle cells. Electrophysiologically, lymphatic smooth muscle LSM) exhibits intrinsic pacemaker properties that allow sponaneous action potential firing, sync hronized contr action w av es, nd facilitation of lymph propulsion against pressure gradients. hile the ion channels r esponsib le for the pacemaker proprties of LSM cells have not been clearly defined, L-type Ca 2 + hannels and ATP-sensiti v e K + (K ATP ) channels are present and rucial for LSM contractility and modulation of spontaneous ontractility, r especti v el y. 1 As well as being present in tissues hroughout the body, K ATP channels are prominently expressed n vascular smooth muscle where they regulate vascular tone nd ther efor e b lood flow. 2–4 Functional K ATP channels ar e a etero-octomeric complex of 4 pore-forming potassium chanel subunits (either Kir6.1 or Kir6.2) and 4 r egulator y sulphonyur ea r ece ptor subunits (either SUR1, SUR2A, or SUR2B). It is now ell esta b lished that the “v ascular smooth m uscle” K ATP chanel is formed of Kir6.1 and SUR2B. 2–4 Evidence from molecular","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9713061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissociation Between Neuronal and Astrocytic Calcium Activity in Response to Locomotion in Mice.","authors":"Anna Fedotova,&nbsp;Alexey Brazhe,&nbsp;Maxim Doronin,&nbsp;Dmytro Toptunov,&nbsp;Evgeny Pryazhnikov,&nbsp;Leonard Khiroug,&nbsp;Alexei Verkhratsky,&nbsp;Alexey Semyanov","doi":"10.1093/function/zqad019","DOIUrl":"https://doi.org/10.1093/function/zqad019","url":null,"abstract":"<p><p>Locomotion triggers a coordinated response of both neurons and astrocytes in the brain. Here we performed calcium (Ca²⁺) imaging of these two cell types in the somatosensory cortex in head-fixed mice moving on the airlifted platform. Ca²⁺ activity in astrocytes significantly increased during locomotion from a low quiescence level. Ca²⁺ signals first appeared in the distal processes and then propagated to astrocytic somata, where it became significantly larger and exhibited oscillatory behaviour. Thus, astrocytic soma operates as both integrator and amplifier of Ca²⁺ signal. In neurons, Ca²⁺ activity was pronounced in quiescent periods and further increased during locomotion. Neuronal Ca²⁺ concentration ([Ca²⁺]_i) rose almost immediately following the onset of locomotion, whereas astrocytic Ca²⁺ signals lagged by several seconds. Such a long lag suggests that astrocytic [Ca²⁺]_i elevations are unlikely to be triggered by the activity of synapses among local neurons. Ca²⁺ responses to pairs of consecutive episodes of locomotion did not significantly differ in neurons, while were significantly diminished in response to the second locomotion in astrocytes. Such astrocytic refractoriness may arise from distinct mechanisms underlying Ca²⁺ signal generation. In neurons, the bulk of Ca²⁺ enters through the Ca²⁺ channels in the plasma membrane allowing for steady-level Ca²⁺ elevations in repetitive runs. Astrocytic Ca²⁺ responses originate from the intracellular stores, the depletion of which affects subsequent Ca²⁺ signals. Functionally, neuronal Ca²⁺ response reflects sensory input processed by neurons. Astrocytic Ca²⁺ dynamics is likely to provide metabolic and homeostatic support within the brain active milieu.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9713065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Towards Astroglia-based Noradrenergic Hypothesis of Alzheimer's Disease.","authors":"Giampiero Leanza,&nbsp;Robert Zorec","doi":"10.1093/function/zqac060","DOIUrl":"https://doi.org/10.1093/function/zqac060","url":null,"abstract":"1Dept. of Drug and Health Sciences, University of Catania, Piazza Università, 2, 95131 Catania, Italy, 2Laboratory of Neuroendocrinology-Molecular Cell Physiology, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia and 3Laboratory of Cell Engineering, Celica Biomedical, 1000 Ljubljana, Slovenia ∗Address correspondence to R.Z. (e-mail: robert.zorec@mf.uni.lj.si)","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/82/eb/zqac060.PMC9789502.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10680269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial ATP Production is Required for Endothelial Cell Control of Vascular Tone.","authors":"Calum Wilson,&nbsp;Matthew D Lee,&nbsp;Charlotte Buckley,&nbsp;Xun Zhang,&nbsp;John G McCarron","doi":"10.1093/function/zqac063","DOIUrl":"https://doi.org/10.1093/function/zqac063","url":null,"abstract":"<p><p>Arteries and veins are lined by nonproliferating endothelial cells that play a critical role in regulating blood flow. Endothelial cells also regulate tissue perfusion, metabolite exchange, and thrombosis. It is thought that endothelial cells rely on ATP generated via glycolysis, rather than mitochondrial oxidative phosphorylation, to fuel each of these energy-demanding processes. However, endothelial metabolism has mainly been studied in the context of proliferative cells, and little is known about energy production in endothelial cells within the fully formed vascular wall. Using intact arteries isolated from rats and mice, we show that inhibiting mitochondrial respiration disrupts endothelial control of vascular tone. Basal, mechanically activated, and agonist-evoked calcium activity in intact artery endothelial cells are each prevented by inhibiting mitochondrial ATP synthesis. Agonist-evoked calcium activity was also inhibited by blocking the transport of pyruvate, the master fuel for mitochondrial energy production, through the mitochondrial pyruvate carrier. The role for mitochondria in endothelial cell energy production is independent of species, sex, or vascular bed. These data show that a mitochondrial ATP supply is necessary for calcium-dependent, nitric oxide-mediated endothelial control of vascular tone, and identifies the critical role of endothelial mitochondrial energy production in fueling perfused blood vessel function.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9909368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10799995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing Transgenic Production to Supplementation of ω-3 PUFA Reveals Distinct But Overlapping Mechanisms Underlying Protection Against Metabolic and Hepatic Disorders.","authors":"Noëmie Daniel,&nbsp;Mélanie Le Barz,&nbsp;Patricia L Mitchell,&nbsp;Thibault V Varin,&nbsp;Isabelle Bourdeau Julien,&nbsp;Dominique Farabos,&nbsp;Geneviève Pilon,&nbsp;Josée Gauthier,&nbsp;Carole Garofalo,&nbsp;Jing X Kang,&nbsp;Jocelyn Trottier,&nbsp;Olivier Barbier,&nbsp;Denis Roy,&nbsp;Benoit Chassaing,&nbsp;Emile Levy,&nbsp;Frédéric Raymond,&nbsp;Antonin Lamaziere,&nbsp;Nicolas Flamand,&nbsp;Cristoforo Silvestri,&nbsp;Christian Jobin,&nbsp;Vincenzo Di Marzo,&nbsp;André Marette","doi":"10.1093/function/zqac069","DOIUrl":"https://doi.org/10.1093/function/zqac069","url":null,"abstract":"<p><p>We compared endogenous ω-3 PUFA production to supplementation for improving obesity-related metabolic dysfunction. Fat-1 transgenic mice, who endogenously convert exogenous ω-6 to ω-3 PUFA, and wild-type littermates were fed a high-fat diet and a daily dose of either ω-3 or ω-6 PUFA-rich oil for 12 wk. The endogenous ω-3 PUFA production improved glucose intolerance and insulin resistance but not hepatic steatosis. Conversely, ω-3 PUFA supplementation fully prevented hepatic steatosis but failed to improve insulin resistance. Both models increased hepatic levels of ω-3 PUFA-containing 2-monoacylglycerol and N-acylethanolamine congeners, and reduced levels of ω-6 PUFA-derived endocannabinoids with ω-3 PUFA supplementation being more efficacious. Reduced hepatic lipid accumulation associated with the endocannabinoidome metabolites EPEA and DHEA, which was causally demonstrated by lower lipid accumulation in oleic acid-treated hepatic cells treated with these metabolites. While both models induced a significant fecal enrichment of the beneficial <i>Allobaculum</i> genus, mice supplemented with ω-3 PUFA displayed additional changes in the gut microbiota functions with a significant reduction of fecal levels of the proinflammatory molecules lipopolysaccharide and flagellin. Multiple-factor analysis identify that the metabolic improvements induced by ω-3 PUFAs were accompanied by a reduced production of the proinflammatory cytokine TNFα, and that ω-3 PUFA supplementation had a stronger effect on improving the hepatic fatty acid profile than endogenous ω-3 PUFA. While endogenous ω-3 PUFA production preferably improves glucose tolerance and insulin resistance, ω-3 PUFA intake appears to be required to elicit selective changes in hepatic endocannabinoidome signaling that are essential to alleviate high-fat diet-induced hepatic steatosis.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9909367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9446287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Some Like It Hot: Dynamic Control of Cav2.2 Channels By Chili Peppers.","authors":"Paz Duran,&nbsp;Rajesh Khanna","doi":"10.1093/function/zqac066","DOIUrl":"https://doi.org/10.1093/function/zqac066","url":null,"abstract":"Spicy meals causes the production of happy endorphins together with the triggering of heat and pain, similar to a runner’s high. The active ingredient in hot chili peppers that causes their distinctive burning sensation is called capsaicin (8-methylN-vanillyl-6-nonenamide). This bioactive substance binds to the primary afferent neurons’ transient receptor potential vanilloid 1 (TRPV1) cation channels, which when activated, cause a sensation of heat. Capsaicin has been utilized as a tool to study the regulation of pain since TRPV1 channels have been reported to be crucial for heat nociception.1 Despite reports that capsaicin binding to TRPV1 channels causes pain, it has been demonstrated that prolonged exposures to capsaicin can desensitize dorsal root ganglion (DRG) neurons, thus reducing afferent drive and reducing synaptic transmission in the dorsal horn.2 Several studies have established that voltage-gated calcium channels (VGCCs) are key modulators of nociceptive and nociplastic pain.3 VGCCs are transmembrane proteins composed of a principal pore-forming α subunit that mediates Ca2+ entry into the cell in response to membrane potential changes. Based on their biophysical characteristics, VGCCs are classified into low voltage activated (LVA) and high voltage activated (HVA) families. HVA channels are typically expressed with auxiliary subunits β and α2δ that regulate the trafficking and function of these channels. The N-type calcium channel, also known as CaV2.2, is a member of the HVA family that is expressed at high levels in sensory neurons where they are key mediators of neurotransmitter release and the transmission of sensory information from the periphery to central sites.4 Given that CaV2.2 channels are the main presynaptic VGCCs and have a critical role in regulating nociceptive transmission, it is reasonable to predict a regulation mediated by capsaicin and TRPV1. However, little is known about the underlying mechanisms of the functional interaction between these channels and their presynaptic function. This gap in knowledge was explored in a very ingenious way by Krishma Ramgoolam and Annette Dolphin in a new study reported in this issue of FUNCTION.5The authors build on their long-standing expertise of N-type calcium channels (CaV2.2) to investigate their functional presynaptic expression and explore their interaction with TRPV1 channels in primary nociceptors. Here, the Dolphin group used their previously described CaV2.2 HA knock-in mouse line, which expresses CaV2.2 with a hemagglutinin (HA) exofacial epitope tag to easily localize endogenous CaV2.2 channels.5 Using co-cultures of DRG neurons isolated from CaV2.2 HA knock-in mice with spinal cord neurons from wild-type (WT) mice and approaches, including immunofluorescence staining and calcium imaging, this study investigated the neuronal maturation, synapse formation, distribution, and presynaptic function of the tagged Ntype calcium channels. First, CaV2.2 localization during n","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9825713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10740530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ion Channel Lateral Diffusion Reveals the Maturation Process of the Neuronal Actin Cytoskeleton.","authors":"Luis A Pardo","doi":"10.1093/function/zqad029","DOIUrl":"https://doi.org/10.1093/function/zqad029","url":null,"abstract":"mall-conductance calcium-acti v ated potassium (SK) channels r e v olta ge-inde pendent K + channels that acti v ate in r esponse o a rise in cytoplasmic Ca 2 + 1 . In neurons, they are, therefore, b le to r educe Ca 2 + entr y in spines and dendrites, limiting proonged depolarization. SK channels can also be found in the oma and in axons, where they likely contribute to spike freuency adaptation. Gu and colleagues used single-particle tr ac kng 2 of SK channels in different areas of pyramidal hippocamal neurons in cultures of different ages. The diffusion coefcient of SK channels was determined along the maturation rocess of the neuronal culture using biotinylated apamin and tr e ptavidin-conjugated quantum dots to label the channels in ombination with total internal reflection microscopy. At the ame time, actin cytoskeleton integrity was manipulated pharacologically to investigate its impact on the diffusion velocity f SK channels. The approach allowed tracking the diffusion of he channel in different compartments, which served as a proxy o determine the stability of actin cytoskeletal structures. Since ta b le actin filaments limited the distribution of SK channels, it as possib le to infer how structured the actin cytoskeleton was long the maturation pr ocess. Importantl y, the submembrane ctin cytoskeleton is incr easingl y r egarded as a crucial factor for odulating the activity of ion channels and transporters at the lasma membrane (see Morache vska ya and Sudarikova 3 ). Neuronal function critically depends on the cytoar c hitecture f the neuron. The cytoskeleton plays a critical role in mainaining the proper neural computation that goes far beyond er e mechanical sta bility and shape maintenance. Specialized tructures crucial for neurotransmission, such as the node of anvier, the axon initial segment (AIS), or synaptic terminals, are","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9713063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}