Neurosignals最新文献

{"title":"Stimulation of Anxiety-Like Behavior via ERK Pathway by Competitive Serotonin Receptors 2A and 1A in Post-Traumatic Stress Disordered Mice.","authors":"Mingjun Xiang,&nbsp;Yuting Jiang,&nbsp;Zhiying Hu,&nbsp;Yang Yang,&nbsp;Benson O A Botchway,&nbsp;Marong Fang","doi":"10.1159/000481791","DOIUrl":"https://doi.org/10.1159/000481791","url":null,"abstract":"<p><strong>Background/aims: </strong>Serotonin 5HT2A and 5HT1A receptors (5HT2AR, 5HT1AR) have the closest connection to anxiety-like behavior in post-traumatic stress disorder (PTSD). However, the underlying mechanism remains unclear. In this study, we explored the connection between 5HT2A and 5HT1A receptors and anxiety-like behavior.</p><p><strong>Methods: </strong>In the PTSD animal model, mice were exposed to conditioned fear stress coupled with single-prolonged stress (CF+SPS). Post stress infliction and behavioral tests, of which include open field, freezing behavior and elevated plus maze tests were carried out to examine establishment of the proposed model. Both Western blot analysis and immunofluorescence labeling were used to evaluate protein expressions of 5HT2AR, 5HT1AR, ERK1, ERK2 and c-Myc in the hippocampi of the mice and RT Q-PCR was employed for evaluation of the relative mRNA expressions.</p><p><strong>Results: </strong>Based on the model established utilizing the CF+SPS procedure, we found 5HT2AR to play a positive role on anxiety-like behavior by inhibiting the expression of 5HT1AR. In addition, the ERK-c-Myc pathway elicited the effect of 5HT2AR and 5HT1AR on anxiety-like behavior in PTSD, 5-HT enhanced the anxiety-like behavior through both 5HT2AR and 5HT1AR.</p><p><strong>Conclusion: </strong>These findings suggest competive interaction between 5HT2AR and 5HT1AR actively affects anxiety-like behavior in the hippocampi of PTSD mice via the ERK pathway.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"25 1","pages":"39-53"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000481791","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35571781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decreased Fronto-Parietal and Increased Default Mode Network Activation is Associated with Subtle Cognitive Deficits in Elderly Controls.","authors":"Davide Zanchi,&nbsp;Marie-Louise Montandon,&nbsp;Indrit Sinanaj,&nbsp;Cristelle Rodriguez,&nbsp;Antoinette Depoorter,&nbsp;Francois R Herrmann,&nbsp;Stefan Borgwardt,&nbsp;Panteleimon Giannakopoulos,&nbsp;Sven Haller","doi":"10.1159/000486152","DOIUrl":"https://doi.org/10.1159/000486152","url":null,"abstract":"<p><strong>Background: </strong>Cognitive functions progressively deteriorate during aging and neurodegenerative diseases. The present study aims at investigating differences in working memory performance as well as functional brain changes during the earliest stages of cognitive decline in health elderly individuals.</p><p><strong>Methods: </strong>62 elderly individuals (41 females), including 41 controls (35 females) and 21 middle cognitive impairment subjects (6 females), underwent neuropsychological assessment at baseline and an fMRI examination in a N-back paradigm contrasting 2-back vs. 0-back condition. Upon a 18 months follow-up, we identified stable controls (sCON) with preserved cognition and deteriorating controls (dCON) with -1SD decrease of performances in at least two neuropsychological tests. Data analyses included accuracy and reaction time (RT) for the 2-back condition and general linear model (GLM) for the fMRI sequence.</p><p><strong>Results: </strong>At the behavioral level, sCON and dCON performed better than MCI in terms of accuracy and reaction time. At the brain level, functional differences in regions of the fronto-parietal network (FPN) and of the Default Mode Network (DFM) were observed. Significantly lower neural activations in the bilateral inferior and middle frontal gyri were found in MCI versus both dCON / sCON and for dCON versus sCON. Significantly increased activations in the anterior cingulate cortex and posterior cingulate cortex and bilateral insula were found in MCI versus both dCON / sCON and in dCON versus sCON.</p><p><strong>Conclusion: </strong>The present study suggests that brain functional changes in FPN and DMN anticipate differences in cognitive performance in healthy elderly individuals with subsequent subtle cognitive decline.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"25 1","pages":"127-138"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000486152","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35680575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Spatial Extent of Epiretinal Electrical Stimulation in the Healthy Mouse Retina.","authors":"Zohreh Hosseinzadeh,&nbsp;Archana Jalligampala,&nbsp;Eberhart Zrenner,&nbsp;Daniel Lleweylln Rathbun","doi":"10.1159/000479459","DOIUrl":"https://doi.org/10.1159/000479459","url":null,"abstract":"<p><strong>Background/aims: </strong>Retinal prostheses use electrical stimulation to restore functional vision to patients blinded by retinitis pigmentosa. A key detail is the spatial pattern of ganglion cells activated by stimulation. Therefore, we characterized the spatial extent of network-mediated electrical activation of retinal ganglion cells (RGCs) in the epiretinal monopolar electrode configuration.</p><p><strong>Methods: </strong>Healthy mouse RGC activities were recorded with a micro-electrode array (MEA). The stimuli consisted of monophasic rectangular cathodic voltage pulses and cycling full-field light flashes.</p><p><strong>Results: </strong>Voltage tuning curves exhibited significant hysteresis, reflecting adaptation to electrical stimulation on the time scale of seconds. Responses decreased from 0 to 300 µm, and were also dependent on the strength of stimulation. Applying the Rayleigh criterion to the half-width at half-maximum of the electrical point spread function suggests a visual acuity limit of no better than 20/946. Threshold voltage showed only a modest increase across these distances.</p><p><strong>Conclusion: </strong>The existence of significant hysteresis requires that future investigations of electrical retinal stimulation control for such long-memory adaptation. The spread of electrical activation beyond 200 µm suggests that neighbouring electrodes in epiretinal implants based on indirect stimulation of RGCs may be indiscriminable at interelectrode spacings as large as 400 µm.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"25 1","pages":"15-25"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000479459","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35199932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Depression in the Context of Medical Disorders: New Pharmacological Pathways Revisited.","authors":"Undine E Lang,&nbsp;Marc Walter","doi":"10.1159/000482001","DOIUrl":"https://doi.org/10.1159/000482001","url":null,"abstract":"<p><p>The depressive state has been characterised as one of elevated inflammation, changed cardiovascular parameters and a deranged metabolic situation all of which holds promise for a better understanding and handling of treatment-resistance in affective disorders as well as for future developments in treatment algorithms. In this context several biomarkers are differentially regulated by antidepressant treatment and connected to metabolic, inflammatory, cardiovascular and apoptotic components of the pathophysiology, i.e. adiponectin, apolipoprotein-B, B-type natriuretic peptide, cortisol, CRP, cysteine, homocysteine, fibrinogen, adiponectin, BMI, glycated hemoglobin A1c, leptin, interferon-gamma, high-density lipoprotein, interleukin interleukin-1alpha, -1beta, -2, -4, -5, -6, -8, -10, -12, -13, -17, insulin-like growth factor-1, low-density lipoprotein, myeloperoxidase, osteoprotegerin, tumour necrosis factor alpha, troponins, triglycerides etc. In this context antidepressants exert different modulatory effects on the outcome, incidence and mortality concerning several severe disorders, i.e. cancer, diabetes, stroke, inflammation, stroke and cardiovascular risk. Vice versa different drugs used in the treatment of these disorders have a favourable effect in depressive states, e.g. statins, aspirine, NSAIDs, pioglitazone, celecoxib, peroxisome proliferator-activated receptor-gamma agonists and minocycline. In this review, actions of different antidepressant treatment strategies on cancer, stroke, diabetes and cardiovascular disorders are shown and the influence on the outcome of the disorders is differentially discussed. In conclusion a hypothetic model for the implication of actual findings in everyday clinical practice is proposed. In this context personalized treatment could be used to tailor treatment to specific individuals according to their clinical endophenotypes. Moreover a potential target for the development of novel intervention strategies might be used.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"25 1","pages":"54-73"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000482001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35458857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endomorphins: Promising Endogenous Opioid Peptides for the Development of Novel Analgesics.","authors":"Zheng-Hui Gu,&nbsp;Bo Wang,&nbsp;Zhen-Zhen Kou,&nbsp;Yang Bai,&nbsp;Tao Chen,&nbsp;Yu-Lin Dong,&nbsp;Hui Li,&nbsp;Yun-Qing Li","doi":"10.1159/000484909","DOIUrl":"https://doi.org/10.1159/000484909","url":null,"abstract":"<p><p>Endomorphin-1 (EM1) and endomorphin-2 (EM2) are two endogenous ligands that belong to the opioid peptide family and have the highest affinity and selectivity for the µ-opioid receptor (MOR). The neuroanatomical distribution, ultrastructural features and neural circuitry of EM-containing neuronal structures have been morphologically demonstrated. In addition, the modulation effects of the EMs in different areas reflect their potential endogenous roles in many major physiological processes, including their remarkable roles in the transmission and modulation of noxious information. The distinguished antinociceptive property of the EMs in acute and chronic pain, including neuropathic pain, cancer pain and inflammatory pain, has been revealed and investigated for therapeutic purposes. However, EMs exert adverse effects in the gastrointestinal, urinary, cardiovascular, and respiratory systems, which impede the development of EMs as new analgesics. Numerous studies have synthesized and investigated EM analogues and demonstrated that these EM derivatives had improved pharmacological properties, supporting their therapeutic perspectives. In the present review, the results of previous studies, particularly morphological and pharmacological studies, were summarized. Finally, EM modifications and their potential clinical implications were described. Applying this knowledge about EMs may provide information for further investigations in clinical application.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"25 1","pages":"98-116"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000484909","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35548034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improved Neural Regeneration with Olfactory Ensheathing Cell Inoculated PLGA Scaffolds in Spinal Cord Injury Adult Rats.","authors":"Changxing Wang,&nbsp;Chenglong Sun,&nbsp;Zhiying Hu,&nbsp;Xue Huo,&nbsp;Yang Yang,&nbsp;Xuehong Liu,&nbsp;Benson O A Botchway,&nbsp;Henry Davies,&nbsp;Marong Fang","doi":"10.1159/000471828","DOIUrl":"https://doi.org/10.1159/000471828","url":null,"abstract":"<p><strong>Background/aims: </strong>Every year, around the world, between 250000 and 500000 people suffer from spinal cord injury (SCI). This study investigated the potential for poly (lactic-co-glycolic acid) (PLGA) complex inoculated with olfactory ensheathing cells (OECs) to treat spinal cord injury in a rat model.</p><p><strong>Methods: </strong>OECs were identified by immunofluorescence based on the nerve growth factor receptor (NGFR) p75. The Basso, Beattie, and Bresnahan (BBB) score, together with an inclined plane (IP) test were used to detect functional recovery. Nissl staining along with the luxol fast blue (LFB) staining were independently employed to illustrate morphological alterations. More so, immunofluorescence labeling of the glial fibrillary acidic protein (GFAP) and the microtubule-associated protein-2 (MAP-2), representing astrocytes and neurons respectively, were investigated at time points of weeks 2 and 8 post-operation.</p><p><strong>Results: </strong>The findings showed enhanced locomotor recovery, axon myelination and better protected neurons post SCI when compared with either PLGA or untreated groups (P < 0.05).</p><p><strong>Conclusion: </strong>PLGA complexes inoculated with OECs improve locomotor functional recovery in transected spinal cord injured rat models, which is most likely due to the fact it is conducive to a relatively benevolent microenvironment, has nerve protective effects, as well as the ability to enhance remyelination, via a promotion of cell differentiation and inhibition of astrocyte formation.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"25 1","pages":"1-14"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000471828","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34869893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increase of Substance P Concentration in Saliva after Pharyngeal Electrical Stimulation in Severely Dysphagic Stroke Patients - an Indicator of Decannulation Success?","authors":"Paul Muhle,&nbsp;Sonja Suntrup-Krueger,&nbsp;Stefan Bittner,&nbsp;Tobias Ruck,&nbsp;Inga Claus,&nbsp;Thomas Marian,&nbsp;Jens B Schröder,&nbsp;Jens Minnerup,&nbsp;Tobias Warnecke,&nbsp;Sven G Meuth,&nbsp;Rainer Dziewas","doi":"10.1159/000482002","DOIUrl":"https://doi.org/10.1159/000482002","url":null,"abstract":"<p><strong>Background/aims: </strong>Substance P (SP) is a neuropeptide, likely acting as a neurotransmitter in the pharyngeal mucosa enhancing the swallow and cough reflex. Pharyngeal Electrical Stimulation (PES) induces a temporary increase of salivary SP levels in healthy adults. Previous evidence suggests that post-stroke dysphagia is related to reduced SP levels. Here, we investigated the effects of PES on SP levels in severely dysphagic stroke patients and a possible link between increase of SP and treatment success.</p><p><strong>Methods: </strong>23 tracheotomized stroke patients who could not be decannulated due to severe and persisting dysphagia according to endoscopic evaluation received PES for 10 minutes a day over three consecutive days in this prospective single-center study. If initial treatment failed, repetitive stimulation cycles were provided. Saliva samples were collected before and directly after each PES.</p><p><strong>Results: </strong>61% of participants were decannulated after the first treatment cycle. Increase of SP levels post-stimulation was closely related to treatment success, i.e. decannulation with 79% of successfully treated patients showing increase of SP, whereas 89% of unsuccessfully treated patients had stable or decreased SP levels. Applying logistic regression analysis, increase of SP level remained the only independent predictor of decannulation after PES. All 3 repetitively treated patients showed increased SP levels when progressing from the 1st to the 2nd cycle, two of whom were decannulated hereafter.</p><p><strong>Conclusions: </strong>The physiological mechanism of PES may consist in restoration of sensory feedback, which is known to be crucial for the execution of a safe swallow. SP possibly acts as a biomarker for indicating response to PES.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"25 1","pages":"74-87"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000482002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35458859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blockade of Experimental Multiple Sclerosis by Inhibition of the Acid Sphingomyelinase/Ceramide System.","authors":"Katrin Anne Becker,&nbsp;Ramona Halmer,&nbsp;Laura Davies,&nbsp;Brian D Henry,&nbsp;Regan Ziobro-Henry,&nbsp;Yann Decker,&nbsp;Yang Liu,&nbsp;Erich Gulbins,&nbsp;Klaus Fassbender,&nbsp;Silke Walter","doi":"10.1159/000484621","DOIUrl":"https://doi.org/10.1159/000484621","url":null,"abstract":"<p><strong>Background: </strong>Multiple sclerosis (MS) is a severe and common autoimmune disorder of the central nervous system. Despite the availability of several novel treatment options, the disease is still poorly controlled, since the pathophysiological mechanisms are not fully understood.</p><p><strong>Methods: </strong>We tested the role of the acid sphingomyelinase/ceramide system in a model of MS, i.e. experimental autoimmune encephalomyelitis (EAE). Mice were immunized with myelin-oligodendrocyte glycoprotein and the development of the disease was analyzed by histology, immunological tests and clinical assessment in wildtype and acid sphingomyelinase (Asm)-deficient mice.</p><p><strong>Results: </strong>Genetic deficiency of acid sphingomyelinase (Asm) protected against clinical symptoms in EAE and markedly attenuated the characteristic detrimental neuroinflammatory response. T lymphocyte adhesion, integrity of tight junctions, blood-brain barrier disruption and subsequent intracerebral infiltration of inflammatory cells were blocked in Asm-deficient mice after immunization. This resulted in an almost complete block of the development of disease symptoms in these mice, while wildtype mice showed severe neurological symptoms typical for EAE.</p><p><strong>Conclusion: </strong>Activation of the Asm/ceramide system is a central step for the development of EAE. Our findings may serve to identify novel therapeutic strategies for MS patients.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"25 1","pages":"88-97"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000484621","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35247765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the Potassium Channel Kv1.3 Kills Glioblastoma Cells.","authors":"Elisa Venturini,&nbsp;Luigi Leanza,&nbsp;Michele Azzolini,&nbsp;Stephanie Kadow,&nbsp;Andrea Mattarei,&nbsp;Michael Weller,&nbsp;Ghazaleh Tabatabai,&nbsp;Michael J Edwards,&nbsp;Mario Zoratti,&nbsp;Cristina Paradisi,&nbsp;Ildikò Szabò,&nbsp;Erich Gulbins,&nbsp;Katrin Anne Becker","doi":"10.1159/000480643","DOIUrl":"https://doi.org/10.1159/000480643","url":null,"abstract":"<p><strong>Background/aims: </strong>Glioblastoma (GBM) is one of the most aggressive cancers, counting for a high number of the newly diagnosed patients with central nervous system (CNS) cancers in the United States and Europe. Major features of GBM include aggressive and invasive growth as well as a high resistance to treatment. Kv1.3, a potassium channel of the shaker family, is expressed in the inner mitochondrial membrane of many cancer cells. Inhibition of mitochondrial Kv1.3 was shown to induce apoptosis in several tumor cells at doses that were not lethal for normal cells.</p><p><strong>Methods: </strong>We investigated the expression of Kv1.3 in different glioma cell lines by immunocytochemistry, western blotting and electron microscopy and analyzed the effect of newly synthesized, mitochondria-targeted, Kv1.3 inhibitors on the induction of cell death in these cells. Finally, we performed in vivo studies on glioma bearing mice.</p><p><strong>Results: </strong>Here, we report that Kv1.3 is expressed in mitochondria of human and murine GL261, A172 and LN308 glioma cells. Treatment with the novel Kv1.3 inhibitors PAPTP or PCARBTP as well as with clofazimine induced massive cell death in glioma cells, while Psora-4 and PAP-1 were almost without effect. However, in vivo experiments revealed that the drugs had no effect on orthotopic brain tumors in vivo.</p><p><strong>Conclusion: </strong>These data serve as proof of principle that Kv1.3 inhibitors kills GBM cells, but drugs that act in vivo against glioblastoma must be developed to translate these findings in vivo.</p>","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"25 1","pages":"26-38"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000480643","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35470502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SGK3 Sensitivity of Large-Conductance Ca2+-Activated K+ Channel","authors":"Musaab Ahmed, Myriam Fezai, F. Lang","doi":"10.1159/000442618","DOIUrl":"https://doi.org/10.1159/000442618","url":null,"abstract":"Background/Aims: Large conductance Ca²⁺-activated K⁺ channels (maxi K⁺ channels or BK channels) are rapidly activated by increase of cytosolic Ca²⁺ activity. The channels participate in the regulation of diverse functions including neuronal excitation and cell volume. The BK channels may be modified by kinases. Channel regulating kinases include the serum & glucocorticoid inducible kinase 3 (SGK3). The present study explored whether SGK3 modifies the activity of BK channels. Methods: cRNA encoding the Ca²⁺ insensitive BK channel mutant BK^{M513I+Δ899-903} was injected into Xenopus laevis oocytes without or with additional injection of cRNA encoding wild-type SGK3, constitutively active ^S419DSGK3, or catalytically inactive ^K191NSGK3. K⁺ channel activity was measured utilizing dual electrode voltage clamp. Results: BK channel activity in BK^{M513I+Δ899-903} expressing oocytes was significantly increased by co-expression of SGK3 or active ^S419DSGK3, but not by coexpression of inactive ^K191NSGK3. Conclusion: SGK3 is a novel positive regulator of BK channels, and thus participates in the regulation of cell volume and excitability.","PeriodicalId":19171,"journal":{"name":"Neurosignals","volume":"24 1","pages":"113 - 124"},"PeriodicalIF":0.0,"publicationDate":"2016-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000442618","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"64982608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}