- Ion channel regulation and function
- Ion Transport and Channel Regulation
- Neuroscience and Neuropharmacology Research
- Cardiac electrophysiology and arrhythmias
- Ion Channels and Receptors
- Drug Transport and Resistance Mechanisms
- Neuroscience and Neural Engineering
- Clinical Nutrition and Gastroenterology
- Cystic Fibrosis Research Advances
- Nicotinic Acetylcholine Receptors Study
- Amino Acid Enzymes and Metabolism
- Digestive system and related health
- Pancreatic function and diabetes
- Electrochemical Analysis and Applications
- Lipid Membrane Structure and Behavior
- Diet and metabolism studies
- Asymmetric Hydrogenation and Catalysis
- Receptor Mechanisms and Signaling
- Neonatal Respiratory Health Research
- Gastrointestinal motility and disorders
- Connexins and lens biology
- Aldose Reductase and Taurine
- Metabolism and Genetic Disorders
- Muscle metabolism and nutrition
- Neuroscience of respiration and sleep
University of Chile
1996-2024
Centro de Estudios Científicos
2015-2024
San Sebastián University
2022-2024
Center for Research and Advanced Studies of the National Polytechnic Institute
2024
University of Talca
2016
University of Castilla-La Mancha
2007-2016
École Polytechnique Fédérale de Lausanne
2016
Inserm
2014
Sorbonne Université
2014
Instituto Chileno de Medicina Reproductiva
2000
Excitatory synaptic transmission is accompanied by a local surge in interstitial lactate that occurs despite adequate oxygen availability, puzzling phenomenon termed aerobic glycolysis. In addition to its role as an energy substrate, recent studies have shown modulates neuronal excitability acting through various targets, including NMDA receptors and G-protein-coupled specific for lactate, but little known about the cellular molecular mechanisms responsible increase lactate. Using panel of...
Tamoxifen is an antiestrogen frequently used in the treatment of breast cancer and currently being assessed as a prophylactic for those at high risk developing tumors. We have found that tamoxifen its derivatives are high-affinity blockers specific chloride channels. This blockade appears to be independent interaction with estrogen receptor therefore reflects alternative cellular target. One clinical side effects impaired vision cataract. Chloride channels lens eye were shown essential...
The molecular identity of K+channels involved in Ehrlich cell volume regulation is unknown. A background K+ conductance activated by swelling and also modulated extracellular pH. These characteristics are most similar to those newly emerging TASK (TWIK-related acid-sensitive channels)-type two pore-domain channels. mTASK-2, but not TASK-1 or -3, present cells mouse kidney tissue from where the full coding sequences were obtained. Heterologous expression mTASK-2 cDNA HEK-293 generated...
Ruthenium derivatives of the type [RuCl(arene)(NN)][BPh4] (arene = benzene, p-cymene) have been synthesized with NN 2-hydroxyphenylbis(pyrazol-1-yl)methane (bpzmArOH) or 2-hydroxyphenylbis(3,5-dimethylpyrazol-1-yl)methane (bpz*mArOH). In p-cymene derivative containing bpzmArOH, activation hydroxy group is observed and a scorpionate complex obtained ligand behaving in tridentate manner, [Ru(bpzmArO-κ3-N,N,O)(p-cymene)][BPh4]. The structure this that [RuCl(p-cymene)(bpz*mArOH)][BPh4] were...
The Cl– channel ClC-2 is expressed in transporting epithelia and has been proposed as an alternative route for efflux that might compensate the malfunction of CFTR cystic fibrosis. There controversy concerning cellular membrane location ClC-2, particularly intestinal tissue. aim this paper to resolve by immunolocalization studies using tissues from knockout animals control, ascertaining sorting model epithelial cells exploring possible molecular signals involved targeting. was exclusively...
Potassium channels share a common selectivity filter that determines the conduction characteristics of pore. Diversity in K+ is given by how they are gated open. TASK-2, TALK-1, and TALK-2 two-pore region (2P) KCNK open extracellular alkalinization. We have explored mechanism for this alkalinization-dependent gating using molecular simulation site-directed mutagenesis followed functional assay. show side chain single arginine residue (R224) near pore senses pH TASK-2 with an unusual pKa 8.0,...
1. An autoradiographic technique is described whereby the cellular location of tritiated amino acids can be determined following uptake by rabbit ileal mucosa. 2. Stirring solutions in contact with intestinal mucosa during measurement rapid influx changes quantity, but not distribution, alanine taken up tissue. 3. Conditions predicted to favour either a high affinity system (Ly1) or low (Ly2) were used measure lysine distribution uptake. Maximal for both transport systems occurred fully...
1. Influx of neutral and basic amino acids into the mucosal epithelium rabbit ileum was measured in presence high low concentrations Na. Uptake at an acid concentration 1 mM varied from 10 to 16 nmole . cm-2 min-1. Removal Na inhibited uptake short-chain more than long-chain acids. 2. Inhibition glycine, alanine, leucine phenylalanine by a selection non-radioactive found follow particular pattern. Long-chain all test acids; preferentially glycine. 3. The maximum inhibition serine could cause...
TASK-2 (KCNK5 or K2P5.1) is a background K+ channel that opened by extracellular alkalinization and plays role in renal bicarbonate reabsorption central chemoreception. Here, we demonstrate addition to its regulation protons (pHo) gated open intracellular alkalinization. The following pieces of evidence suggest the gating process controlled pH (pHi) independent from under command pHo. It was not possible overcome closure acidification means mutant TASK-2-R224A lacks sensitivity pHo had...
Organic osmolyte and halide permeability pathways activated in epithelial HeLa cells by cell swelling were studied radiotracer efflux techniques single-cell volume measurements. The replacement of extracellular Cl- anions that are more permeant through the volume-activated channel, as indicated electrophysiological measurements, significantly decreased taurine efflux. In presence less-permeant anions, an increase was observed. Simultaneous measurement 125I, used a tracer for Cl-, [3H]taurine...
Functional and structural studies demonstrate that Cl − channels of the ClC family have a dimeric double‐barrelled structure, with each monomer contributing an identical pore. Single protopore gating is fast process dependent on interaction within selectivity filter in ClC‐0 has low temperature coefficient over 10°C range ( Q 10 ). A slow closes both protopores simultaneously, high , facilitated by extracellular Zn 2+ Cd abolished or markedly reduced mutation cysteine conserved ClC‐0, ‐1 ‐2....
The ClC-2 Cl- channel has been postulated to play a role in the inhibitory GABA response neurons or participate astrocyte-dependent extracellular electrolyte homeostasis. Three different mutations CLCN2 gene, encoding voltage-dependent homodimeric channel, have associated with idiopathic generalized epilepsy (IGE). We study their function vitro by patch clamp and confocal microscopy transiently transfected HEK-293 cells. A first mutation predicts premature stop codon (M200fsX231). An altered...
ClC-2 is a ubiquitously expressed, two-pore homodimeric Cl- channel opened by hyperpolarisation. Little known about its gating mechanisms. Crystallographic and functional studies in other ClC channels suggest that conserved glutamate residue carboxylate side-chain can close protopores interacting with Cl--binding site the pore. Competition for this thought to provide molecular basis extracellular Cl-. We now show depends upon intra- but not neutralisation of E217, homologous pore glutamate,...
Intestinal fluid secretion is driven by apical membrane, cystic fibrosis transmembrane conductance regulator (CFTR)‐mediated efflux of Cl– that concentrated in cells basolateral Na + −K −2Cl– cotransporters (NKCC1). An absolute requirement for the parallel activation K channels which maintain a membrane potential sustains anion secretion. Both cAMP and Ca 2+ are intracellular signals intestinal The channel involved cAMP‐dependent has been identified as KCNQ1–KCNE3 complex, but identity...
Abstract A new and safer methodology has been developed for the synthesis of bis(pyrazol‐1‐yl)methane ligands (NN). Several containing different phenyl groups on central carbon atom have obtained. Ruthenium derivatives type [Ru(arene)Cl(NN)]BPh 4 (arene = benzene, p ‐cymene) synthesised using these ligands. One or two isomers that differ regarding axial equatorial disposition group metallacycle Their formation is rationalised by considering steric effects. The structures five were determined...