A5062893427- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Neuroscience and Neural Engineering
- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- Cardiac Ischemia and Reperfusion
- Electrochemical Analysis and Applications
- Analytical Chemistry and Sensors
- Cardiac pacing and defibrillation studies
- Fatty Acid Research and Health
- Nicotinic Acetylcholine Receptors Study
- Cardiomyopathy and Myosin Studies
- Eicosanoids and Hypertension Pharmacology
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Ion Channels and Receptors
- Nitric Oxide and Endothelin Effects
- Analytical Methods in Pharmaceuticals
- Pharmacological Effects and Assays
- Pulmonary Hypertension Research and Treatments
- Wound Healing and Treatments
- Immune cells in cancer
- Diabetic Foot Ulcer Assessment and Management
- Neuroblastoma Research and Treatments
- Lipid Membrane Structure and Behavior
- Sphingolipid Metabolism and Signaling
Hospital Universitario de La Princesa
2022-2025
Universidad Autónoma de Madrid
2015-2025
Instituto de Investigaciones Biomédicas Sols-Morreale
2014-2024
Consejo Superior de Investigaciones Científicas
2002-2024
Instituto de Salud Carlos III
2019-2023
Universitat de Barcelona
2014-2023
Centro de Investigación en Red en Enfermedades Cardiovasculares
2019-2023
Centro de Investigación Biomédica en Red
2021-2023
Consorci Institut D'Investigacions Biomediques August Pi I Sunyer
2023
Instituto de Cibernética Matemática y Física
2023
Background Bupivacaine is a potent local anesthetic widely used for prolonged and regional anesthesia. However, accidental intravascular injection of bupivacaine can produce severe arrhythmias cardiac depression. Although clinically as racemic mixture, S (−)-bupivacaine appears less toxic than the R (+)-enantiomer despite at least equal potency If more in blocking sodium channels, then (−)-enantiomer could be with chance cardiovascular toxicity. Therefore, we tested whether such...
Deregulated protein and Ca2+ homeostasis underlie synaptic dysfunction neurodegeneration in Huntington disease (HD); however, the factors that disrupt are not fully understood. Here, we determined expression of downstream regulatory element antagonist modulator (DREAM), a multifunctional Ca2+-binding protein, is reduced murine vivo vitro HD models patients. DREAM downregulation was observed early after birth associated with endogenous neuroprotection. In R6/2 mouse model, induced...
Abstract The mechanism of inhibition Na + channels by lidocaine has been suggested to involve low-affinity binding rested states and high-affinity the inactivated state channel, implying either multiple receptor sites or allosteric modulation affinity. Alternatively, may be guarded channel gates. To test these distinct hypotheses, was studied voltage-clamp methods in both native heterologous expression systems. Native were guinea pig ventricular myocytes, recombinant human heart expressed...
Voltage-dependent potassium (Kv) channels play a pivotal role in the modulation of macrophage physiology. Macrophages are professional antigen-presenting cells and produce inflammatory immunoactive substances that modulate immune response. Blockage Kv by specific antagonists decreases cytokine production inhibits proliferation. Numerous pharmacological agents exert their effects on target modifying activity plasma membrane ion channels. Investigation mechanisms involved regulation conduction...
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,...
Diabetic foot ulcer is a principal diabetic complication. It has been shown that patients have decreased growth factor concentrations in their tissues, particularly epidermal factor. Growth shortage impairs wound healing, which leads to chronic nonhealing wounds and sometimes eventual amputation. Ischemic the most difficult treat confers highest amputation risk.
Resolution of inflammation is orchestrated by specialized proresolving lipid mediators (SPMs), and this would be impaired in some cardiovascular diseases. Among SPMs, resolvins (Rv) have beneficial effects pathologies, but little known about their effect on damage hypertension.Aorta, small mesenteric arteries, heart, peritoneal macrophages were taken from C57BL/6J mice, infused or not with angiotensin II (AngII; 1.44 mg/kg/day, 14 days) presence absence resolvin D2 (RvD2) (100 ng/mice, every...
Background Zatebradine is a bradycardic agent that inhibits the hyperpolarization-activated current (I f ) in rabbit sinoatrial node. It also prolongs action potential duration papillary muscles guinea pigs and Purkinje fibers rabbits. The underlying mechanism by which zatebradine induces this effect has not been explored, but it likely to involve K + channel block. Methods Results Cloned human cardiac delayed rectifier currents (hKv1.5) were recorded Ltk − cells transfected with their...
Dietary n-3 polyunsaturated fatty acids (PUFAs) have been reported to exhibit antiarrhythmic properties, and these effects attributed their capability modulate ion channels. In the present review, we will focus on of PUFAs a cardiac sodium channel (Na(v)1.5) two potassium channels involved in atrial ventricular repolarization (K(v)) (K(v)1.5 K(v)11.1). marine (docosahexaenoic, DHA eicosapentaenoic acid, EPA) plant origin (alpha-linolenic ALA) block K(v)1.5 K(v)11.1 at physiological...
Abstract Enantiomers of local anesthetics are useful probes ion channel structure that can reveal three-dimensional relations for drug binding in the pore and may have important clinical consequences. Bupivacaine block open hKv1.5 channels is stereoselective, with R (+)-enantiomer being 7-fold more potent than S (−)-enantiomer ( K d =4.1 μmol/L versus 27.3 μmol/L). Using whole-cell voltage clamp site-directed mutants stably expressed Ltk − cells, we identified a set amino acids determine...
Background —The effects of type 1 angiotensin II receptor antagonist losartan and its metabolite E3174 on transmembrane action potentials, hKv1.5, HERG, I Ks currents were analyzed. Methods Results —Guinea pig ventricular potentials recorded with microelectrode techniques hKv1.5 HERG the whole-cell patch-clamp technique. was in guinea myocytes perforated-nystatin-patch configuration. Losartan transiently increased current by 8.0±1.4% 7.4±1.6%, respectively. Thereafter, they produced a...
Background— It has been demonstrated that spironolactone (SP) decreases the QT dispersion in chronic heart failure. In this study, effects of SP and its metabolite, canrenoic acid (CA), on human ether-a-go-go–related gene (HERG) currents were analyzed. Methods Results— HERG elicited stably transfected Chinese hamster ovary cells measured with whole-cell patch-clamp technique. decreased a concentration-dependent manner (IC 50 =23.0±1.5 μmol/L) shifted midpoint activation curve to more...
Potassium channels modulate macrophage physiology. Blockade of voltage-dependent potassium (Kv) by specific antagonists decreases cytokine production and inhibits proliferation. In the presence aspirin, acetylated cyclooxygenase-2 loses activity required to synthesize PGs but maintains oxygenase produce 15R-HETE from arachidonate. This intermediate product is transformed via 5-LOX into epimeric lipoxins, termed 15-epi-lipoxins (15-epi-lipoxin A4 [e-LXA4]). Kv have been proposed as...
Experimental evidence indicates that the control of inflammatory response after myocardial infarction is a key strategy to reduce cardiac injury. Cellular damage blood flow restoration in heart promotes sterile inflammation through release molecules activate pattern recognition receptors, among which TLR4 most prominent. Transient regulation activity has been considered one potential therapeutic interventions with greater projection towards clinic. In this regard, characterization an aptamer...
We studied the effects of irbesartan, a selective angiotensin II type 1 receptor antagonist, on human <i>ether-a-go-go</i>-related gene (HERG), KvLQT1+minK, hKv1.5, and Kv4.3 channels using patch-clamp technique. Irbesartan exhibited low affinity for HERG KvLQT1+minK (IC<sub>50</sub> = 193.0 ± 49.8 314.6 85.4 μM, respectively). In hKv1.5 channels, irbesartan produced two types block, depending concentration tested. At 0.1 inhibited current in time-dependent manner (22 3.9% at +60 mV). The...
Objective: The aim of this study was to analyze the effects loratadine on a human cardiac K+ channel (hKv1.5) cloned from ventricle and stably expressed in mouse cell line. Methods: Currents were studied using whole-cell configuration patch−clamp technique Ltk− cells transfected with gene encoding hKv1.5 channels. Results: Loratadine inhibited concentration-dependent manner current, apparent affinity being 1.2±0.2 μM. blockade increased steeply between −30 0 mV which corresponded voltage...
Abstract The effects of propafenone on the delayed rectifier K + current were studied in guinea pig ventricular myocytes by using patch-clamp technique. In these myocytes, this consists at least two components: a La 3+ -sensitive component activating rapidly with moderate depolarizations and -resistant slowly more positive potentials. absence (when both components are present), inhibited outward current, its being marked after weak than strong depolarizations. Propafenone-induced block tail...
To understand better the cerebral functions, several methods have been developed to study brain activity, they could be related with morphological, electrophysiological, molecular and neurochemical techniques. Monitoring neurotransmitter concentration is a key role know how works during normal or pathological conditions, as well for studying changes in use of drugs that affect reestablish activity. Immediate response environmental conditions release fast acting neurotransmission by glutamate...
The NO/cGMP pathway represents a major physiological signalling controlling tone in pulmonary arteries (PA), and drugs activating this are used to treat arterial hypertension. Kv channels expressed PA smooth muscle cells (PASMCs) key determinants of vascular tone. We aimed analyse the contribution 1.5 7 electrophysiological vasodilating effects evoked by NO donors GC stimulator riociguat PA.Kv currents were recorded isolated rat PASMCs using patch-clamp technique. Vascular reactivity was...
Levobupivacaine and ropivacaine are the pure S(−) enantiomers of N‐butyl‐ N‐propyl‐2′,6′‐pipecoloxylidide, developed as less cardiotoxic alternatives to bupivacaine. In present study, we have analysed effects levobupivacaine, bupivacaine on HERG channels stably expressed in CHO cells. The three drugs blocked a concentration‐, time‐ state‐dependent manner. Block measured at end 5 s pulses −10 mV induced by 20 μ M (52.7±2.0%, n =15) (55.5±2.7%, =13) was similar ( P >0.05) both lower than...
1. The goal of this study was to analyse the effects propafenone and its major metabolite, 5-hydroxy-propafenone, on a human cardiac K+ channel (hKv1.5) stably expressed in Ltk- cells using whole-cell configuration patch-clamp technique. 2. Propafenone 5-hydroxy-propafenone inhibited concentration-dependent manner hKv1.5 current with K(D) values 4.4+/-0.3 microM 9.2+/-1.6 microM, respectively. 3. Block induced by both drugs voltage-dependent consistent value electrical distance (referenced...