A5014334385- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Neuroscience and Neural Engineering
- Cardiac Arrhythmias and Treatments
- Atrial Fibrillation Management and Outcomes
- Cardiac pacing and defibrillation studies
- Receptor Mechanisms and Signaling
- Heart Failure Treatment and Management
- Cardiomyopathy and Myosin Studies
- Pharmacology and Obesity Treatment
- Hormonal Regulation and Hypertension
- Neuroscience and Neuropharmacology Research
- Potassium and Related Disorders
- Electrochemical Analysis and Applications
- Nitric Oxide and Endothelin Effects
- Cardiac Ischemia and Reperfusion
- Analytical Methods in Pharmaceuticals
- RNA Research and Splicing
- Diabetes Treatment and Management
- Cardiovascular Function and Risk Factors
- Eicosanoids and Hypertension Pharmacology
- Cancer Treatment and Pharmacology
- Pharmacogenetics and Drug Metabolism
- RNA regulation and disease
- Blood Pressure and Hypertension Studies
Hospital General Universitario Gregorio Marañón
2016-2025
Universidad Complutense de Madrid
2016-2025
Centro de Investigación Biomédica en Red
2017-2025
Centro de Investigación en Red en Enfermedades Cardiovasculares
2017-2025
Instituto de Salud Carlos III
2022-2025
Centro de Investigación Biomédica en Red de Cáncer
2024
Hospital Universitario de Getafe
2002-2018
Weatherford College
2009-2012
Hospital de Sant Pau
2011
Universidad de Jaén
2011
The Brugada Syndrome (BrS), an inherited syndrome associated with a high incidence of sudden cardiac arrest, has been linked to mutations in four different genes leading loss function sodium and calcium channel activity. Although the transient outward current (I(to)) is thought play prominent role expression syndrome, I(to)-related have not identified as yet.One hundred five probands BrS were screened for ion gene using single strand conformation polymorphism (SSCP) electrophoresis direct...
Background— Pitx2 is a homeobox transcription factor that plays pivotal role in early left/right determination during embryonic development. loss-of-function mouse mutants display lethality with severe cardiac malformations, demonstrating the importance of cardiogenesis. Recently, independent genome-wide association studies have provided new evidence for putative PITX2 adult heart. These independently reported several risk variants close to locus on chromosome 4q25 are strongly associated...
Rationale: In cardiomyocytes, Na V 1.5 and Kir2.1 channels interact dynamically as part of membrane bound macromolecular complexes. Objective: The objective this study was to test whether preassemble during early forward trafficking travel together common microdomains. Methods Results: patch-clamp experiments, coexpression trafficking-deficient mutants Δ314-315 or R44A/R46A with wild-type (WT) WT in heterologous cells reduced inward sodium current compared alone coexpressed . cell surface...
Background— Atrial fibrillation is characterized by progressive atrial structural and electrical changes (atrial remodeling) that favor arrhythmia recurrence maintenance. Reduction of L-type Ca 2+ current ( I Ca,L ) density a hallmark the remodeling. Alterations in microRNAs could contribute to protein underlying fibrillation–induced This study was undertaken compare miR-21 levels isolated myocytes from appendages obtained patients sinus rhythm with chronic (CAF) determine whether channel...
Cardiac excitability and refractoriness are largely determined by the function number of inward rectifier K+ channels (Kir2.1–2.3), which differentially expressed in atria ventricles, Nav1.5 channels. We have focused on how Kir2.x within a macromolecular complex elucidating molecular determinants that govern Nav1.5/Kir2.x reciprocal modulation. The results demonstrate there is an unexpected 'internal' PDZ-like binding domain located at N-terminus channel mediates its to α1-syntrophin....
In a family with inappropriate sinus tachycardia (IST), we identified mutation (p.V240M) of the hyperpolarization-activated cyclic nucleotide–gated type 4 (HCN4) channel, which contributes to pacemaker current (I f ) in human sinoatrial node cells. Here, clinically study fifteen members and functionally analyze p.V240M variant. Macroscopic HCN4 single-channel currents were recorded using patch-clamp cells expressing native (WT) and/or channels. All carriers exhibited IST that was accompanied...
Both increase and decrease of cardiac inward rectifier current (I(K1)) are associated with severe arrhythmias. Flecainide, a widely used antiarrhythmic drug, exhibits ventricular proarrhythmic effects while effectively controlling arrhythmias mutations in the gene encoding Kir2.1 channels that I(K1) (Andersen syndrome). Here we characterize electrophysiological molecular basis flecainide-induced generated by (I(Kir2.1)) recorded myocytes. Flecainide increases outward I(Kir2.1) homotetrameric...
Atrial fibrillation (AF) produces rapid changes in the electrical properties of atria (electrical remodelling) that promote its own recurrence. In chronic AF (CAF) patients, up-regulation slow delayed rectifier K+ current (IKs) and down-regulation voltage-gated Ca2+ (ICa,L) are hallmarks remodelling critically contribute to abbreviation action potential duration atrial refractory period. Recent evidences suggested Pitx2c, a bicoid-related homeodomain transcription factor involved directing...
The effect of circulating biomarkers in predicting coronary artery disease (CAD) is not fully elucidated. This study aimed to determine the relationship with CAD and predictive capacity nine inflammation (TNF-α, IL-10, IL-6, MCP-1, CRP), oxidation (GHS-Px), metabolism (adiponectin, leptin, insulin). was a case-cohort study, within REGICOR population-cohorts (North-Eastern Spain), 105 cases 638 individuals randomly selected from cohort 5,404 participants aged 35-74 years (mean follow-up = 6.1...
Significance Defective prelamin A processing causes cardiovascular alterations and premature death in Hutchinson–Gilford progeria syndrome (HGPS) patients also occurs during physiological aging. We found overt repolarization abnormalities HGPS at advanced disease stages. Similar were present progeroid Zmpste24 −/− mice, which had cardiomyocytes that exhibited prolonged calcium transient duration reduced sarcoplasmic reticulum loading capacity release, consistent with absence of...
The cardiac inwardly rectifying K(+) current (I(K1)) plays a critical role in modulating excitability by setting the resting membrane potential and shaping phase 3 of action potential.This study aims to analyze effects nitric oxide (NO) on human atrial I(K1) Kir2.1 channels, major isoform channels present heart.Currents were recorded enzymatically isolated myocytes transiently transfected CHO cells, respectively. NO at myocardial physiological concentrations (25 500 nmol/L) increased inward...
The present study analysed the effects of flavanol ( − )-epicatechin in rats after chronic inhibition NO synthesis with N G -nitro- l -arginine methyl ester -NAME), at doses equivalent to those achieved studies involving human subjects. Wistar were randomly divided into four groups: (1) control-vehicle, (2) -NAME, (3) -NAME-epicatechin 2 -NAME-Epi 2) and (4) 10 10). Rats daily given by oral administration for 4 weeks: vehicle, or mg/kg. Animals -NAME groups received 75 mg/100 ml...
β-adrenergic stimulation has profound influence in the genesis and maintenance of atrial fibrillation (AF). However, effects β-Adrenoceptor on repolarizing currents action potential (AP) characteristics human myocytes from left (LAA) right appendages (RAA) obtained sinus rhythm (SR) chronic (CAF) patients have not been compared yet. Currents APs were recorded using whole-cell patch-clamp RAA LAA SR CAF patients. Isoproterenol concentration-dependently decreased Ca2+-independent...
Cardiac Nav1.5 and Kir2.1-2.3 channels generate Na (INa) inward rectifier K (IK1) currents, respectively. The functional INa IK1 interplay is reinforced by the positive reciprocal modulation between Nav15 Kir2.1/2.2 to strengthen control of ventricular excitability. Loss-of-function mutations in SCN5A gene, which encodes channels, underlie several inherited arrhythmogenic syndromes, including Brugada syndrome (BrS). We investigated whether presence BrS-associated alters density concomitantly...
Cardiac Kir2.1 and Nav1.5 channels generate the inward rectifier K+ (IK1) Na+ (INa) currents, respectively. There is a mutual interplay between ventricular INa IK1 densities, because exhibit positive reciprocal modulation. Here we compared some of biological properties when they are expressed together or separately to get further insights regarding their putative interaction. First demonstrated by proximity ligation assays that in membrane myocytes proteins close each other (<40 nm apart)....
Significance Tbx20 is a transcription factor whose critical role in cardiogenesis well-established. Here we functionally analyzed the electrophysiological effects produced by mutation (p.R311C) found some affected individuals belonging to family with long QT syndrome (an inherited cardiac arrhythmia due delayed ventricular repolarization). We demonstrated that selectively increases expression of KCNH2 , which encodes for channel Kv11.1 (hERG) generates main repolarizing current. Conversely,...