A5045441577- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Neuroscience and Neural Engineering
- Neuroscience and Neuropharmacology Research
- Cardiac pacing and defibrillation studies
- Cancer therapeutics and mechanisms
- Antibiotic Resistance in Bacteria
- Pluripotent Stem Cells Research
- Nicotinic Acetylcholine Receptors Study
- Neutropenia and Cancer Infections
- Viral Infections and Immunology Research
- RNA Research and Splicing
- Pharmaceutical studies and practices
- Receptor Mechanisms and Signaling
- Bioactive Compounds and Antitumor Agents
- ECG Monitoring and Analysis
- Tissue Engineering and Regenerative Medicine
- 3D Printing in Biomedical Research
- Neurobiology and Insect Physiology Research
- Epilepsy research and treatment
- Analytical Methods in Pharmaceuticals
- Cardiac Arrhythmias and Treatments
- Antibiotics Pharmacokinetics and Efficacy
- Animal Genetics and Reproduction
- Electrochemical Analysis and Applications
United States Military Academy
2014-2024
Merck & Co., Inc., Rahway, NJ, USA (United States)
2008-2024
Fundação Armando Alvares Penteado
2017
Vollum Institute
1992-1998
Oregon Health & Science University
1992-1998
Baylor College of Medicine
1994
Emory University
1989-1991
University of Connecticut
1989
We report here a characterization of two families calcium-activated K+ channel β-subunits, β2 and β3, which are encoded by distinct genes that map to 3q26.2–27. A single family member four alternatively spliced variants β3 were investigated. These subunits have predicted molecular masses 27.1–31.6 kDa, share ∼30–44% amino acid identity with β1, exhibit but overlapping expression patterns. Coexpression the or β3a–c BK α-subunit altered functional properties current expressed alone. The...
The Slowpoke locus of Drosophila melanogaster encodes a family alternatively spliced mRNAs which encode large conductance calcium-activated potassium channels. Variability residues in blocks amino acids designated boxes A, C, E, G, and I. Oocytes were injected with cRNAs that had been chosen for direct functional comparison single box differences. Single channel records from inside-out patches oocyte membranes expressing A1 or A3 forms, E1 E2 G2-G5 forms analyzed compared. main difference...
5-Hydroxytryptamine type 3 receptors were expressed in Xenopus oocytes from a cloned cDNA. The peak inward current evoked by 5-hydroxytryptamine (30 microM) was linearly related to the holding potential (-100 +20 mV) and reversed near 0 mV. (at -60 declined during continued presence of with half-time about 2 s; this desensitization 20 times slower calcium-free solution. Desensitization markedly different channels which Leu286 changed site-directed mutagenesis; residue is thought lie middle...
We have identified a series of diphenyl phosphine oxide (DPO) compounds that are potent frequency-dependent inhibitors cloned human Kv1.5 (hKv1.5) channels. DPO inhibited hKv1.5 expressed in Chinese hamster ovary cells concentration-dependent manner preferentially during channel activation and slowed the deactivating tail current, consistent with predominant open-channel blocking mechanism. Varying kinetics interaction channels resulted differing potencies frequency dependencies inhibition...
Bacterial resistance is eroding the clinical utility of existing antibiotics necessitating discovery new agents. type II topoisomerase a clinically validated, highly effective, and proven drug target. This target amenable to inhibition by diverse classes inhibitors with alternative distinct binding sites quinolone antibiotics, thus enabling development agents that lack cross-resistance quinolones. Described here are novel bacterial (NBTIs), which class gyrase topo IV consist three structural...
1. The regulation of IK and ICa were studied in single cells isolated from bull‐frog atrium using the whole‐cell configuration patch clamp a perfused pipette. 2. was increased approximately 50‐100% 6‐10 times by 1 microM‐isoprenaline, 5 microM‐forskolin, or internal perfusion with 30 microM‐cyclic AMP. effects cyclic AMP isoprenaline not additive. shape concentration‐response curves EC50 values for on very similar (2.3 microM 1.7 ICa). 3. Elevation intracellular had effect regardless whether...
Vorinostat (SAHA, Zolinza), a histone deacetylase inhibitor, is assessed in nonclinical studies to support its approval for cutaneous T-cell lymphoma. weakly mutagenic the Ames assay; clastogenic rodent (ie, CHO) cells but not normal human lymphocytes; and positive an vivo mouse micronucleus assay. No effects are observed on potassium ion currents hERG assay up 300 μM (safety margin ~300-fold ~1 serum concentration associated with 400 mg/d maximum recommended dose. rat respiratory or central...
There is critical need for a predictive model of human cardiac physiology in drug development to assess compound effects on tissues. In vitro two-dimensional monolayer cultures cardiomyocytes provide biochemical and cellular readouts, vivo animal models information systemic cardiovascular response. However, there remains significant gap these due their incomplete recapitulation adult physiology. Recent efforts developing from engineered heart tissues have demonstrated potential bridging this...
The goal of this research consortium including Janssen, MSD, Ncardia, FNCR/LBR, and Health Environmental Sciences Institute (HESI) was to evaluate the utility an additional in vitro assay technology detect potential drug-induced long QT torsade de pointes (TdP) risk by monitoring cytosolic free Ca2+ transients human stem-cell-derived cardiomyocytes (hSC-CMs). proarrhythmic risks 28 comprehensive proarrhythmia (CiPA) drugs linked low, intermediate, high clinical TdP were evaluated a blinded...