A5023531626- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Neuroscience of respiration and sleep
- Neuroscience and Neuropharmacology Research
- Ion Channels and Receptors
- Nitric Oxide and Endothelin Effects
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Hemoglobin structure and function
- Cardiomyopathy and Myosin Studies
- High Altitude and Hypoxia
- Sodium Intake and Health
- Ion Transport and Channel Regulation
- Cardiac Ischemia and Reperfusion
- Sleep and Wakefulness Research
- Cell Adhesion Molecules Research
- Lipid Membrane Structure and Behavior
- Neuroscience and Neural Engineering
- Cardiac Fibrosis and Remodeling
- Cancer, Hypoxia, and Metabolism
- RNA Research and Splicing
- Parathyroid Disorders and Treatments
- Angiogenesis and VEGF in Cancer
- interferon and immune responses
- Receptor Mechanisms and Signaling
- Renin-Angiotensin System Studies
Universidad de Valladolid
2016-2025
Instituto de Biomedicina y Genética Molecular de Valladolid
2016-2025
Consejo Superior de Investigaciones Científicas
2014-2025
Mexican Social Security Institute
2018
Lund University
2015
Universitat de Barcelona
2005-2010
Unidades Centrales Científico-Técnicas
2009
Johns Hopkins University
1995-1997
Johns Hopkins Medicine
1995-1997
Gram-negative bacterial infections are accompanied by inflammation and somatic or visceral pain. These symptoms generally attributed to sensitization of nociceptors inflammatory mediators released immune cells. Nociceptor during occurs through activation the Toll-like receptor 4 (TLR4) signalling pathway lipopolysaccharide (LPS), a toxic by-product lysis. Here we show that LPS exerts fast, membrane delimited, excitatory actions via TRPA1, transient potential cation channel is critical for...
Mutations in human LPIN2 produce a disease known as Majeed syndrome, the clinical manifestations of which are ameliorated by strategies that block IL-1β or its receptor. However role lipin-2 during production remains elusive. We show here controls excessive formation primary and mouse macrophages several mechanisms, including activation inflammasome NLRP3. Lipin-2 regulates MAPK activation, mediates synthesis pro-IL-1β priming. also inhibits sensitization purinergic receptor P2X7 K+ efflux,...
Voltage-gated K+ (KV) channels are protein complexes composed of ion-conducting integral membrane α subunits and cytoplasmic modulatory β subunits. The differential expression association seems to contribute significantly the complexity heterogeneity KV in excitable cells, their functional heterologous systems provides a tool study regulation at molecular level. Here, we have studied effects Kvβ1.2 coexpression on properties Shaker Kv4.2 channel subunits, which encode rapidly inactivating...
Hypoxic inhibition of large-conductance Ca(2+)-dependent K(+) channels (maxiK) rat carotid body type I cells is a well-established fact. However, the molecular mechanisms such and role these in process hypoxic transduction remain unclear. We have examined interaction O(2) with maxiK exploring effect hypoxia on currents recorded whole-cell inside-out configuration patch-clamp technique. Hypoxia inhibits channel activity both excised membrane patches. This strongly voltage- Ca(2+)-dependent,...
1. Upon depolarization, voltage‐gated sodium channels assume non‐conducting inactivated states which may be characterized as ‘fast’ or ‘slow’ depending on the length of repolarization period needed for recovery. Skeletal muscle Na+ channel alpha‐subunits expressed in Xenopus laevis oocytes display anomalous gating behaviour, with substantial slow inactivation after brief depolarizations. We exploited this kinetic behaviour to examine structural basis inactivation. 2. While fast is mediated...
Native cardiac and skeletal muscle Na channels are complexes of alpha beta 1 subunits. While structural correlates for activation, inactivation, permeation have been identified in the subunit expression alone produces functional channels, 1-deficient rat (mu 1) brain expressed Xenopus oocytes do not gate normally. In contrast, requirement a normal function cloned from heart or human (hH1) has disputed. Coinjection cRNA with hH1 (or mu into increased peak currents recorded 2 d after injection...
Objective— Phenotypic modulation of vascular smooth muscle cells has been associated with a decreased expression all voltage-dependent potassium channel (Kv)1 encoding genes but Kcna3 (which encodes Kv1.3 channels). In fact, upregulation currents seems to be important modulate proliferation mice femoral in culture. This study was designed explore if these changes Kv1 pattern constituted landmark phenotypic across beds and investigate the mechanisms involved proproliferative function...
The functions of macrophages are tightly regulated by their metabolic state. However, the role mitochondrial electron transport chain (ETC) in macrophage remains understudied. Here, we provide evidence that succinate dehydrogenase (SDH)/complex II (CII) is required for respiration and plays a controlling effector responses macrophages. We find absence catalytic subunits Sdha Sdhb impairs ability to effectively stabilize HIF-1α produce pro-inflammatory cytokine IL-1β response LPS stimulation....
The pores of voltage-gated cation channels are formed by four intramembrane segments that impart selectivity and conductance. Remarkably little is known about the higher order structure these critical pore-lining or P segments. Serial cysteine mutagenesis reveals a pattern side-chain accessibility contradicts currently favored structural models based on alpha-helices beta-strands. Like active sites many enzymes structure, sodium channel pore consists irregular loop regions.
We used serial cysteine mutagenesis to study the structure of outer vestibule and selectivity region voltage-gated Na+ channel. The voltage dependence Cd2+ block enabled us determine locations within electrical field cysteine-substituted mutants in P segments all four domains. fractional distances substituted cysteines were compared with differential sensitivity modification by sulfhydryl-specific modifying reagents. These experiments indicate that segment domain II is external, while IV...
This study aimed to identify novel isoforms of mouse succinate dehydrogenase complex flavoprotein subunit A (Sdha) arising from internal exon skipping, analogous the process observed in human ortholog SDHA. We identified a isoform, designated Δ3-10, which lacked final 104 nucleotides 3 and all exons 4 through 10, yet did not alter reading frame. The Δ3-10 Sdha cDNA was cloned into expression vectors, overexpression resulted protein localized mitochondria. However, endogenous detected with...
As there are wide interspecies variations in the molecular nature of O(2)-sensitive Kv channels arterial chemoreceptors, we have characterized expression these and their hypoxic sensitivity mouse carotid body (CB). CB chemoreceptor cells were obtained from a transgenic expressing green fluorescent protein (GFP) under control tyrosine hydroxylase (TH) promoter. Immunocytochemical identification TH cell cultures reveals good match with GFP-positive cells. Furthermore, show an increase...
1. Coexpression of the beta subunit with alpha 1C cardiac L‐type Ca2+ channel has been shown to increase ionic current. To examine mechanism this increase, and gating currents were measured in transiently transfected HEK293 cells. 2. Beta 1A coexpression increased maximal whole‐cell conductance (Gmax) 10 mM Ba2+ from 91 +/‐ 11 833 107 pS pF‐1 without a change voltage dependence activation (V1/2: ‐6.1 1.1 ‐6.6 0.9 mV, respectively). 3. Gating smaller cells expressing only (only four out...
1. The electrical properties of chemoreceptor cells from neonatal rat and adult rabbit carotid bodies (CBs) are strikingly different. These differences have been suggested to be developmental and/or species related. To distinguish between the two possibilities, whole‐cell configuration patch‐clamp technique was used characterize ionic currents present in isolated CBs. Since hypoxia‐induced inhibition O2‐sensitive K+ is considered a crucial step O2 chemoreception, effect hypoxia on cell also...
Rabbit carotid body (CB) chemoreceptor cells possess a fast‐inactivating K + current that is specifically inhibited by hypoxia. We have studied the expression of Kvα subunits, which might be responsible for this current. RT‐PCR experiments identified Kv1.4, Kv3.4, Kv4.1 and Kv4.3 mRNAs in rabbit CB. There was no Kv3.3 or Kv4.2 transcripts. Immunocytochemistry with antibodies to tyrosine hydroxylase (anti‐TH) specific Kv subunits revealed Kv3.4 cells, while Kv1.4 only found nerve fibres. mRNA...
The cardiac dihydropyridine-sensitive calcium channel was transiently expressed in HEK293 cells by transfecting the rabbit alpha 1 subunit (alpha 1C) alone or combination with beta cloned from skeletal muscle. Transfection 1C leads to expression of inward, voltage-activated, barium currents that exhibit dihydropyridine sensitivity and voltage- as well calcium-dependent inactivation. Coexpression muscle increases current density number high-affinity binding sites also affects macroscopic...
Ion permeation and channel gating are classically considered independent processes, but site-specific mutagenesis studies in K channels suggest that residues or near the ion-selective pore of can influence activation inactivation. We describe a mutation skeletal muscle Na alters gating. This mutation, I-W53C (residue 402 mu 1 sequence), decreases sensitivity to block by tetrodotoxin increases externally applied Cd2+ relative wild-type channel, placing this residue within external mouth....
Vascular smooth muscle cells (VSMCs) contribute significantly to occlusive vascular diseases by virtue of their ability switch a noncontractile, migratory, and proliferating phenotype. Although the participation ion channels in this phenotypic modulation (PM) has been described previously, changes expression are poorly defined because large molecular diversity. We obtained global portrait channel contractile versus mouse femoral artery VSMCs, explored functional contribution PM most relevant...
Actin dynamics in vascular smooth muscle is known to regulate contractile differentiation and may play a role the pathogenesis of disease. However, list genes regulated by actin polymerization remains incomprehensive. Thus, objective this study was identify actin-regulated demonstrate these regulation phenotype.Mouse aortic cells were treated with an actin-stabilizing agent, jasplakinolide, analyzed microarrays. Several transcripts upregulated including both previously unknown genes....