A5047125139- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Neuroscience and Neuropharmacology Research
- Planarian Biology and Electrostimulation
- Neuroscience and Neural Engineering
- bioluminescence and chemiluminescence research
- Neurological Disease Mechanisms and Treatments
- interferon and immune responses
- RNA Research and Splicing
- Neurological Disorders and Treatments
- RNA regulation and disease
- Fatty Acid Research and Health
- Cardiac Ischemia and Reperfusion
- Ion Transport and Channel Regulation
- ATP Synthase and ATPases Research
- Advanced Fluorescence Microscopy Techniques
- Alzheimer's disease research and treatments
- Click Chemistry and Applications
- Developmental Biology and Gene Regulation
- Plant and Biological Electrophysiology Studies
- Plant Molecular Biology Research
- Photoreceptor and optogenetics research
- Metabolomics and Mass Spectrometry Studies
Universitat de Barcelona
2009-2024
Max Delbrück Center
2021-2024
Leibniz-Forschungsinstitut für Molekulare Pharmakologie
2022
Universidad Autónoma de Madrid
2014
University of the Basque Country
2014
Instituto de Investigaciones Biomédicas Sols-Morreale
2014
Organoids derived from stem cells have become an increasingly important tool for studying human development and modeling disease. However, methods are still needed to control study spatiotemporal patterns of gene expression in organoids. Here we combined optogenetics perturbation technologies activate or knock-down RNA target genes programmable patterns. To illustrate the usefulness our approach, locally activated Sonic Hedgehog (SHH) signaling organoid model neurodevelopment. Spatial...
Abstract Herpes simplex encephalitis is a life-threatening disease of the central nervous system caused by herpes viruses (HSVs). Following standard care with antiviral acyclovir treatment, most patients still experience various neurological sequelae. Here we characterize HSV-1 infection human brain organoids combining single-cell RNA sequencing, electrophysiology and immunostaining. We observed strong perturbations tissue integrity, neuronal function cellular transcriptomes. Under treatment...
Voltage-dependent potassium channels (Kv) play a crucial role in the activation and proliferation of leukocytes. Kv are either homo- or hetero-oligomers. This composition modulates their surface expression serves as mechanism for regulating channel activity. interaction with accessory subunits provides mechanisms to respond stimuli beyond changes membrane potential. Here, we demonstrate that KCNE4 (potassium voltage-gated subfamily E member 4), but not KCNE2, functions an inhibitory Kv1.3...
KCNQ1 and KCNE1 encode Kv7.1 KCNE1, respectively, the pore-forming accessory subunits of slow delayed rectifier potassium current, IKs. mutations are associated with long short QT syndrome. The aim this study was to characterize biophysical cellular phenotype a missense mutation, F279I, found in 23-year-old man corrected interval (QTc) 356 ms family history sudden cardiac death. Experiments were performed using perforated patch-clamp, western blot, co-immunoprecipitation, biotinylation,...
The KCNQ1 (Kv7.1) channel plays an important role in cardiovascular physiology. Cardiomyocytes co-express with KCNE1-5 proteins. may co-associate multiple KCNE regulatory subunits to generate different biophysically and pharmacologically distinct channels. Increasing evidence indicates that the location targeting of channels are determinants their function. In this context, presence K(+) sphingolipid-cholesterol-enriched membrane microdomains (lipid rafts) is under investigation. Lipid rafts...
Voltage-dependent K(+) (Kv) channels from the Kv7 family are expressed in blood vessels and contribute to cardiovascular physiology. Although channel blockers trigger muscle contractions, activators act as vasorelaxants. Kv7.1 Kv7.5 many vessels. is under intense investigation because fail modulate smooth reactivity. In this study, we analyzed whether may form functional heterotetrameric increasing diversity vascular muscles.Kv7.1 currents elicited arterial myocytes, oocyte, mammalian...
Polyunsaturated fatty n-3 acids (PUFAs) have been reported to exhibit antiarrhythmic properties. However, the mechanisms of action remain unclear. We studied electrophysiological effects eicosapentaenoic acid (EPA) and docosahexaenoic (DHA) on IKs, expression location Kv7.1 KCNE1. Experiments were performed using patch-clamp, western blot, sucrose gradient techniques in COS7 cells transfected with Kv7.1/KCNE1 channels. Acute perfusion both PUFAs increased current, this effect being greater...
Volume-regulated anion channels (VRACs) are heterohexamers of LRRC8A with LRRC8B, -C, -D, or -E in various combinations. Depending on the subunit composition, these swelling-activated conduct chloride, amino acids, organic osmolytes, and drugs. Despite VRACs' role cell volume regulation, large osmolarity changes kidney, neither localization nor function VRACs kidney is known.Mice expressing epitope-tagged LRRC8 subunits were used to determine renal all VRAC subunits. Mice carrying...
Abstract Aim The voltage‐gated Kv7.1 channel, in association with the regulatory subunit KCNE1, contributes to I Ks current heart. However, both proteins travel plasma membrane using different routes. While KCNE1 follows a classical Golgi‐mediated anterograde pathway, is located endoplasmic reticulum‐plasma junctions (ER‐PMjs), where it associates before being delivered membrane. Methods To characterize channel routing these spots we used wide repertoire of methodologies, such as protein...
Kv7 (KCNQ) proteins form a family of voltage-gated potassium channels that is comprised five members, Kv7.1-Kv7.5. While Kv7.1 crucial in the heart, Kv7.2, Kv7.3, Kv7.4 and Kv7.5 contribute to M-current nervous system. In addition brain, expressed skeletal smooth muscle, where its physiological role currently under evaluation. associations with KCNE accessory subunits (KCNE1-5) enhance channel diversity their interaction provides mechanisms respond variety stimuli. peptides control surface...
The potassium channel Kv7.1 associates with the KCNE1 regulatory subunit to trigger cardiac I Ks currents. Although Kv7.1/KCNE1 complex has received much attention, subcellular compartment hosting assembly is subject of ongoing debate. Evidence suggests that forms either earlier in endoplasmic reticulum or directly at plasma membrane. and mutations, responsible for long QT syndromes, impair association traffic, thereby altering We found do not assemble first stages their biogenesis. Data...
Abstract Organoids derived from stem cells become increasingly important to study human development and model disease. However, methods are needed control spatio-temporal patterns of gene expression in organoids. To this aim, we combined optogenetics perturbation technologies activate or knock-down RNA target genes, at single-cell resolution programmable patterns. illustrate the usefulness our approach, locally activated Sonic Hedgehog ( SHH ) signaling an organoid for neurodevelopment....
Abstract Herpes simplex virus type 1 (HSV-1) infection of the nervous system may lead to brain damage, including neurodegeneration. However, lack suitable experimental models hinders understanding molecular mechanisms and cell-type-specific responses triggered by HSV-1. Here, we infected human organoids with Known features HSV-1 such as alteration neuronal electrophysiology induction antisense transcription were confirmed. Full-length mRNA-sequencing revealed aberrant 3’ end formation...
Near-infrared ATTO700 is evaluated as an acceptor in SNAP- and Halo-tag protein labelling for ensemble single molecule Förster Resonance Energy Transfer (FRET) stimulated emission by depletion (STED) super resolution microscopy.
Abstract Background: Kv7.5 (KCNQ5) channels conduct M‐type potassium currents in the brain, are expressed skeletal muscle, and contribute to vascular muscle tone. Methods: We coexpressed KCNE1–3 peptides HEK293 cells then analyzed their association using electrophysiology co‐immunoprecipitation, assessed localization confocal microscopy, examined targeting of oligomeric cholesterol‐rich membrane surface microdomains lipid raft isolation, evaluated dynamics fluorescence recovery after...
Voltage-dependent potassium (Kv) channels contribute to the excitability of nerves and muscles. In addition, Kv participates in several cell functions, including cycle progression proliferation. channel remodeling has been associated with neoplastic growth cancer. Kv7 are expressed blood vessels, they participate maintenance vascular tone implicated myocyte Although evidence links different types cancer, its expression tumors never studied. Endothelium-derived neoplasms range from indolent...
Abstract Background In Alzheimer’s disease (AD), intraneuronal tau protein accumulation into neurofibrillary tangles correlates with clinical signs and neurodegeneration 1 . Besides neurotoxic aggregation, dysregulation of lipid metabolism is emerging as a common mechanism 2 The main regulators in the brain are astrocytes astrocyte‐neuron communication key to provide metabolic support neuron 3 While has been suggested bind lipids 4 , little known about potential tau‐lipid interactions brain,...