A5086541043- Ion channel regulation and function
- Neurotransmitter Receptor Influence on Behavior
- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Cardiac electrophysiology and arrhythmias
- Neuroscience and Neural Engineering
- Forensic Toxicology and Drug Analysis
- Nicotinic Acetylcholine Receptors Study
- Lipid Membrane Structure and Behavior
- Drug Transport and Resistance Mechanisms
- Electrochemical Analysis and Applications
- Amino Acid Enzymes and Metabolism
- Molecular Sensors and Ion Detection
- Biotin and Related Studies
- Analytical Chemistry and Chromatography
- Molecular Junctions and Nanostructures
- Force Microscopy Techniques and Applications
- Muscle metabolism and nutrition
- DNA and Nucleic Acid Chemistry
- Nanopore and Nanochannel Transport Studies
- Lanthanide and Transition Metal Complexes
- Bacterial Genetics and Biotechnology
- Electron Spin Resonance Studies
- Ion Channels and Receptors
- Pharmacological Effects and Assays
Medical University of Vienna
2016-2025
Institute of Pharmacology
2018-2023
University of Vienna
2001-2015
National Institute on Drug Abuse
2015
Yale University
2015
National Institutes of Health
2015
Institute of Molecular Biology and Biophysics
2014
University of Chicago
2005-2014
University of Illinois Chicago
2010
Voltage sensors containing the charged S4 membrane segment display a gating charge vs. voltage ( Q–V ) curve that depends on initial voltage. The voltage-dependent phosphatase (Ci-VSP), which does not have conducting pore, shows same phenomenon and recorded with depolarized is more stable by at least 3 RT . leftward shift of under prolonged depolarization was studied in Ci-VSP using electrophysiological site-directed fluorescence measurements. two components: one traces time course movement...
Serotonin (5-HT) uptake by the human serotonin transporter (hSERT) is driven ion gradients. The stoichiometry of transported 5-HT and ions predicted to result in electroneutral charge movement. However, hSERT mediates a current when challenged with 5-HT. This discrepancy can be accounted for an uncoupled flux. Here, we investigated mechanistic basis currents its relation conformational cycle hSERT. Our observations support conclusion that conducting state underlying flux equilibrium inward...
Determining the structural elements that define substrates and inhibitors at monoamine transporters is critical to elucidating mechanisms underlying these disparate functions. In this study, we addressed question directly by generating a series of N-substituted 3,4-methylenedioxyamphetamine analogs differ only in number methyl substituents on terminal amine group. Starting with 3,4-methylenedioxy-N-methylamphetamine, 3,4-methylenedioxy-N,N-dimethylamphetamine (MDDMA)...
The plasmalemmal monoamine transporters clear the extracellular space from their cognate substrates and sustain cellular stores even during neuronal activity. In some instances, however, enter a substrate-exchange mode, which results in release of intracellular substrate. Understanding what determines switch between these two transport modes demands time-resolved measurements (co-)substrate binding release. Here, we report an electrophysiological investigation solute-binding to human...
Psychostimulants interacting with the dopamine transporter (DAT) can be used illicitly or for treatment of specific neuropsychiatric disorders. However, they also produce severe and persistent adverse events. Often, their pharmacological properties in vitro do not fully correlate to profile vivo. Here, we investigated effects enantiomers pyrovalerone, α-pyrrolidinovalerophenone, 3,4-methylenedioxypyrovalerone as compared traditional psychostimulants cocaine methylphenidate, using a variety...
In 56 patients with multiple trauma ISSs ≥ 33 we prospectively collected data of seven scoring systems (ISS, TS, TRISS, GCS, PTS, APACHE II, SSS) and sequentially determined blood lactate concentrations. These were analyzed in relation to the later developing adult respiratory distress syndrome (ARDS) organ failure (MOF). Twenty-two developed ARDS, 18 MOF. Of mentioned only ISS, SSS predictive subsequent ISS Lactate concentrations at days 2, 3, 4 significantly different between without MOF,...
The concentrative power of the transporters for dopamine (DAT), norepinephrine (NET), and serotonin (SERT) is thought to be fueled by transmembrane Na + gradient, but it conceivable that they can also tap other energy sources, example, membrane voltage and/or K gradient. We have addressed this recording uptake endogenous substrates or fluorescent substrate APP (4-(4-dimethylamino)phenyl-1-methylpyridinium) under control in cells expressing DAT, NET, SERT. shown DAT NET differ from SERT...
Abstract Increasing extracellular levels of serotonin (5-HT) in the brain ameliorates symptoms depression and anxiety-related disorders, e.g., social phobias post-traumatic stress disorder. Recent evidence from preclinical clinical studies established therapeutic potential drugs inducing release 5-HT via 5-HT-transporter. Nevertheless, current releasing compounds under investigation carry risk for abuse deleterious side effects. Here, we demonstrate that S -enantiomers certain...
Clearance of serotonin (5-hydroxytryptamine, 5-HT) from the synaptic cleft after neuronal signaling is mediated by transporter (SERT), which couples this process to movement a Na
Voltage control over enzymatic activity in voltage-sensitive phosphatases (VSPs) is conferred by a voltage-sensing domain (VSD) located the N terminus. These VSDs are constituted four putative transmembrane segments (S1 to S4) resembling those found voltage-gated ion channels. The fourth segment (S4) of VSD contains positive residues that likely function as elements. To study detail how these sense plasma membrane potential, we have focused on five arginines S4 Ciona intestinalis VSP...
Neurotransmitter transporters of the SLC6 family proteins, including human serotonin transporter (hSERT), utilize Na(+), Cl(-), and K(+) gradients to induce conformational changes necessary for substrate translocation. Dysregulation ion movement through monoamine has been shown impact neuronal firing potentials could play a role in pathophysiologies, such as depression anxiety. Despite multiple crystal structures prokaryotic eukaryotic SLC indicating location both (or one) conserved...
ABSTRACT Ibogaine, an alkaloid derived from the African shrub Tabernanthe iboga , has shown promising anti‐addictive properties in animals. Anecdotal evidence suggests that ibogaine is also humans. Thus, it alleviates drug craving and impedes relapse of use. Although not licensed as therapeutic drug, despite may disturb rhythm heart, this currently used anti‐addiction alternative medicine. Here, we report concentrations reduce currents through human ether‐a‐go‐go‐related gene potassium...
The plant alkaloid ibogaine has promising anti-addictive properties. Albeit not licenced as a therapeutic drug, and despite hints that may perturb the heart rhythm, this is used to treat drug addicts. We have recently reported inhibits human ERG (hERG) potassium channels at concentrations similar drugs affinity for several of its known brain targets. Thereby disturb heart's electrophysiology. Here, assess drug's cardiac ion channel profile in more detail, we studied effects congener...
Ibogaine is a psychoactive indole alkaloid. Its use as an antiaddictive agent has been accompanied by QT prolongation and cardiac arrhythmias, which are most likely caused human <i>ether go-go–related</i> gene (hERG) potassium channel inhibition. Therefore, we studied in detail the interaction of ibogaine with hERG channels heterologously expressed mammalian kidney tsA-201 cells. Currents through were blocked regardless whether was applied via extracellular or intracellular solution. The...
The membrane transporters for the monoamines serotonin (SERT) and dopamine (DAT) are prominent targets of various psychoactive substances, including competitive inhibitors, such as tricyclic antidepressants, methylphenidate, cocaine. Upon rapid application a substrate, SERT DAT display an inwardly directed current comprised peak steady-state component. Binding inhibitor to transporter leads reduction amplitude because occupancy by prevents induction substrate. We show that inhibitory effect...
Significance CorA is one of the major Mg 2+ uptake systems in prokaryote, yet mechanism selectivity permeation unknown. In CorA, plays a dual role charge carrier and gating factor. Here, we use electrophysiological recordings on mutant to establish that arises from high-affinity divalent binding at Gly-Met-Asn (GMN) signature motif extracellular loop channel. A repulsion through second incoming accelerates rate while precluding monovalent ion flux. This work establishes as multiion channel...