A5082027756- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Neuroscience and Neural Engineering
- Neuropeptides and Animal Physiology
- Nicotinic Acetylcholine Receptors Study
- Cardiomyopathy and Myosin Studies
- Pain Mechanisms and Treatments
- Ion Channels and Receptors
- Electrochemical Analysis and Applications
- Cardiac pacing and defibrillation studies
- Ion Transport and Channel Regulation
- Pluripotent Stem Cells Research
- Cardiac Arrhythmias and Treatments
- Pharmacological Receptor Mechanisms and Effects
- Neonatal Respiratory Health Research
- Photoreceptor and optogenetics research
- Protein Tyrosine Phosphatases
- Private Equity and Venture Capital
- Neurotransmitter Receptor Influence on Behavior
- Memory and Neural Mechanisms
- Mitochondrial Function and Pathology
- Atrial Fibrillation Management and Outcomes
- Global Peace and Security Dynamics
Tel Aviv University
2015-2024
Arthur M. Sackler Gallery
2010-2011
University of Utah
2007-2008
University of Bristol
2007-2008
Ruhr University Bochum
2008
University of Cologne
2008
Technical University of Munich
2008
Columbia University
2007
Mayo Clinic
2007
University of Copenhagen
2006
The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. provides concise overviews, mostly tabular format, key properties nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links open access knowledgebase source and their ligands (www.guidetopharmacology.org), which more detailed views target ligand properties. Although constitutes over 500 pages, material presented substantially reduced compared...
The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. provides concise overviews, mostly tabular format, key properties approximately 1800 drug targets, and over 6000 interactions with about 3900 ligands. There an emphasis on selective pharmacology (where available), plus links open access knowledgebase source targets their ligands (https://www.guidetopharmacology.org/), which more detailed views target ligand properties. Although constitutes almost...
The antipsychotic drug haloperidol can induce a marked QT prolongation and polymorphic ventricular arrhythmias. In this study, we expressed several cloned cardiac K + channels, including the human ether‐a‐go‐go related gene (HERG) in Xenopus oocytes tested them for their sensitivity. Haloperidol had only little effects on delayed rectifier channels Kv1.1, Kv1.2, Kv1.5 I sK , A‐type channel Kv1.4 inward Kir2.1 (inhibition <6% at 3 μ m haloperidol). contrast, blocked HERG potently with an...
The voltage-dependent M-type potassium current (M-current) plays a major role in controlling brain excitability by stabilizing the membrane potential and acting as brake for neuronal firing. KCNQ2/Q3 heteromeric channel complex was identified molecular correlate of M-current. Furthermore, KCNQ2 KCNQ3 α subunits are mutated families with benign familial neonatal convulsions, form epilepsy. Enhancement currents may provide an important target antiepileptic drug development. Here, we show that...
Elevated extracellular K+ ([K+]o), in the absence of “classical” immunological stimulatory signals, was found to itself be a sufficient stimulus activate T cell β1 integrin moieties, and induce integrin-mediated adhesion migration. Gating voltage-gated channels (Kv1.3) appears crucial “decision-making” step, through which various physiological factors, including elevated [K+]o levels, affect function: opening channel leads function, whereas its blockage prevents it. In support this notion,...
The present work shows that arachidonic acid and some other long chain polyunsaturated fatty acids such as docosahexaenoic acid, which is abundant in fish oil, produce a direct open channel block of the major voltage-dependent K+ (Kv1.5) cloned cardiac cells. inhibitory action these selected seen when they are applied extracellularly but not included patch pipette. Fatty then appear to bind an external site on Kv1.5 structure. Inhibition activity by (acceleration apparent inactivation...
The slow I KS K + channel plays a major role in repolarizing the cardiac action potential and consists of assembly KCNQ1 KCNE1 subunits. Mutations either or genes produce long-QT syndrome, life-threatening ventricular arrhythmia. Here, we show that mutations located C terminus impair calmodulin (CaM) binding, which affects both gating assembly. voltage-dependent macroscopic inactivation dramatically alter forms ternary complex with wild-type Ca 2+ -CaM prevents inactivation, facilitates...
Stress-dependent regulation of cardiac action potential duration is mediated by the sympathetic nervous system and hypothalamic-pituitary-adrenal axis. It accompanied an increased magnitude slow outward potassium ion current, I Ks . KCNQ1 KCNE1 subunits coassemble to form channel. Mutations in either subunit cause long QT syndrome, inherited arrhythmia associated with risk sudden death. Here we demonstrate that exocytosis proteins plasma membrane requires small GTPase RAB11, whereas...
Screening a rat colon cDNA library for aldosterone-induced genes resulted in the molecular cloning of whose corresponding mRNA is strongly induced by dexamethasone, aldosterone, and low NaCl diet. A similar was detected kidney papilla but not brain, heart, or skeletal muscle. Xenopus laevis oocytes injected with cRNA synthesized from this clone, designated CHIF (channel-inducing factor), express K(+)-specific channel activity. The biophysical, pharmacological, regulatory characteristics are...
Single-triggered disassemble dendrimers were recently developed and introduced as a potential platform for multi-prodrug. These unique structural can release all of their tail units through self-immolative chain fragmentation initiated by single cleavage at the dendrimer's core. There are several examples bioactivation first-generation dendritic prodrugs. However, enzymatic activation failed second-generation dendrimers. The hydrophobic large molecular structure prodrugs results in...
Low stringency screening of a Jurkat cDNA library with rat brain K+ channel (RCK1) probe has resulted in the isolation HLK3, voltage-gated channel. In Xenopus oocytes, HLK3 clone directs expression rapidly activating transient outward current similar to type n recorded T cells. The gene is located on short arm human chromosome 1 (p13.3). Polymerase chain reaction was used HIsK from cDNA. shares same sequence previously described genomic (Murai, T., Kazikuka, A., Takumi, Ohkubo, H., and...
The Kv7 subfamily of voltage-dependent potassium channels, distinct from other subfamilies by dint its large intracellular COOH terminus, acts to regulate excitability in cardiac and neuronal tissues. KCNQ1 (Kv7.1), the founding member, encodes a channel subunit directly implicated genetic disorders, such as long QT syndrome, pathology responsible for arrhythmias. We have used recombinant protein preparation terminus probe structure function this domain individual modules. COOH-terminal...
The nature of the opiate modulation adenylate cyclase following acute and chronic agonist exposure has been investigated in rat spinal cord. Using membranes both adult cord cord-dorsal root ganglion cocultures, we found that kappa-opiate receptors are negatively coupled to cyclase. agonists (e.g., U50488) inhibit significantly dose-dependently basal forskolin-stimulated activities, whereas mu delta ineffective. regulatory action is stereospecific requires presence GTP. EGTA treatment plasma...
The pore and gate regions of voltage-gated cation channels have been often targeted with drugs acting as channel modulators. In contrast, the voltage-sensing domain (VSD) was practically not exploited for therapeutic purposes, although it is target various toxins. We recently designed unique diphenylamine carboxylates that are powerful Kv7.2 K + openers or blockers. Here we show a opener, NH29, acts nontoxin gating modifier. NH29 increases currents, thereby producing hyperpolarizing shift...
Alterations in synaptic input, persisting for hours to days, elicit homeostatic plastic changes the axon initial segment (AIS), which is pivotal spike generation. Here, hippocampal pyramidal neurons of both primary cultures and slices, we triggered a unique form AIS plasticity by selectively targeting M-type K+ channels, predominantly localize are essential tuning neuronal excitability. While acute M-current inhibition via cholinergic activation or direct channel block made more excitable,...
I Ks channels are composed of sK and KvLQT1 subunits underly the slowly activating, voltage‐dependent conductance in heart. Although it appears clear that protein affects both biophysical properties regulation channels, its role channel pharmacology is unclear. In present study we demonstrate homopolymeric K + inhibited by blockers 293B, azimilide 17‐β‐oestradiol. However, induced coexpression have a 6–100 fold higher affinity for these blockers. Moreover, activators mefenamic acid DIDS had...
Abstract The aim of the present study has been to characterize regulation by opiates 45Ca2+ influx in rat spinal cord-dorsal root ganglion cocultures. We have demonstrated that K+-induced depolarization, presence Ca2+ channel agonist Bay K8644, stimulated (3-4-fold) via dihydropyridine class voltage-dependent channels. While mu and delta had no effect, kappa opiate agonists (e.g. U50488, dynorphin) profoundly depressed (86% inhibition at 100 microM U50488). action was stereospecific could be...
Abstract In a search for potassium channels involved in light- and clock-regulated leaf movements, we cloned four putative K channel genes from the leaf-moving organs, pulvini, of legume Samanea saman. The S. saman SPOCK1 is homologous to KCO1, an Arabidopsis two-pore-domain channel, SPORK1 similar SKOR GORK, outward-rectifying Shaker-like channels, theS. SPICK1 SPICK2 are AKT2, weakly-inward-rectifying channel. All sequences possess universal K-channel-specific pore signature, TXXTXGYG,...
Physical and emotional stress is accompanied by release of hormones such as the glucocorticoid cortisol. This hormone upregulates serum- glucocorticoid-inducible kinase (SGK)1, which in turn stimulates I(Ks), a slow delayed rectifier potassium current that mediates cardiac action potential repolarization. Mutations I(Ks) channel alpha (KCNQ1, KvLQT1, Kv7.1) or beta (KCNE1, IsK, minK) subunits cause long QT syndrome (LQTS), an inherited arrhythmia associated with increased risk sudden death....