A5058057009- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Cardiac electrophysiology and arrhythmias
- Nicotinic Acetylcholine Receptors Study
- Pain Mechanisms and Treatments
- RNA Research and Splicing
- Electrochemical sensors and biosensors
- Photochromic and Fluorescence Chemistry
- Molecular Sensors and Ion Detection
- Genetic Neurodegenerative Diseases
- Cellular transport and secretion
- Receptor Mechanisms and Signaling
- Ion Channels and Receptors
- RNA and protein synthesis mechanisms
- Neurotransmitter Receptor Influence on Behavior
- Neuroendocrine regulation and behavior
- Hearing, Cochlea, Tinnitus, Genetics
- Neuropeptides and Animal Physiology
- Chemical Synthesis and Analysis
- Genomics and Chromatin Dynamics
- Electrochemical Analysis and Applications
- Wnt/β-catenin signaling in development and cancer
- Mitochondrial Function and Pathology
- Signaling Pathways in Disease
- Neurological disorders and treatments
John Brown University
2023-2024
Brown University
2009-2024
Allen Institute for Brain Science
2022-2024
University of New Hampshire
2016-2022
Providence College
2014-2022
LIDSEN Publishing Inc. (United States)
2021
Peruvian University of Applied Sciences
2021
University of New Hampshire at Manchester
2017
Instituto Tecnologico de Veracruz
2013
Pfizer (United States)
2012
Using exome sequencing and linkage analysis in a three-generation family with unique dominant myoclonus-dystonia-like syndrome cardiac arrhythmias, we identified mutation the CACNA1B gene, coding for neuronal voltage-gated calcium channels CaV2.2. This (c.4166G>A;p.Arg1389His) is disruptive missense outer region of ion pore. The functional consequences were studied using whole-cell single-channel patch recordings. High-resolution analyses at level showed that, when open, R1389H CaV2.2...
Abstract CACNA1I is a candidate schizophrenia risk gene. It encodes the pore-forming human Ca V 3.3 α1 subunit, subtype of voltage-gated calcium channel that contributes to T-type currents. Recently, two de novo missense variations, T797M and R1346H, hCa were identified in individuals with schizophrenia. Here we show but not T797M, associated lower protein levels, reduced glycosylation, membrane surface levels when expressed cell lines compared wild-type. Consistent our biochemical analyses,...
Serotonin (5-HT) is a critical neurotransmitter involved in many neuronal functions, and 5-HT depletion has been linked to several mental diseases. The fast release clearance of serotonin the extracellular space, low analyte concentrations, multitude interfering species make detection challenging. This work presents an electrochemical aptamer-based biosensing platform that can monitor continuously with high sensitivity selectivity. Our sensor showed response time approximately 1 min step...
It has been recently demonstrated that progranulin is overexpressed in ovarian cancer and this protein involved the stimulation of cell proliferation, malignancy, chemoresistance cancer. The goal present study was to establish differences expression among normal, benign, malignant tissues identify signal transduction pathways activated by an line. Compared with benign tumors normal tissue, mRNA were tumors. Survival analysis Kaplan-Meier method showed a correlation between high levels poor...
Ca(V)2.2 (N-type) calcium channels control the entry of into neurons to regulate essential functions but most notably presynaptic transmitter release. channel expression levels are precisely controlled, we know little cellular mechanisms involved. The ubiquitin proteasome system (UPS) is known many synaptic proteins, including elements, optimize efficiency. However, have limited information about ubiquitination Ca(V)2 channels. Here show that proteins ubiquitinated, and elements in proximal...
Presynaptic voltage-gated calcium Ca v 2.2 channels play a privileged role in spinal level sensitization following peripheral nerve injury. Direct and indirect inhibitors of channel activity dorsal horn are analgesic chronic pain states. represent family splice isoforms that expressed different combinations according to cell-type. A pair mutually exclusive exons the encoding Cacna1b gene, e37a e37b, differentially influence morphine analgesia. In mice lack exon e37a, which is enriched...
Abstract Presynaptic Ca V 2.2 channels control calcium entry that triggers neurotransmitter release at both central and peripheral synapses. The Cacna1b gene encodes the α1-pore forming subunit of channels. Distinct subsets splice variants derived from cell-specific alternative splicing pre-mRNA are expressed in specific subpopulations neurons. Four sites alter channel function have been described detail: three cassette exons (e18a, e24a, e31a) a pair mutually exclusive (e37a/e37b). mRNAs...
Abstract Glial and glia‐derived cells express a variety of receptors for neurotransmitters hormones, the majority which evoke both Ca 2+ release from intracellular stores entry across plasma membrane. We investigated links between histamine H 1 receptor activation, influx in human astrocytoma U373 MG cells. Histamine, through receptor‐mediated effect, evoked an increase cytoplasmic free calcium concentration ([Ca ] i ) that occurred two phases: initial, transient, owing to mobilization...
Glutamate (Glu) and histamine (His) are two major neurotransmitters that play many critical roles in brain physiological functions neurological disorders. Therefore, specific sensitive monitoring of Glu His is essential the diagnosis treatment various mental health neurodegenerative Both being non-electroactive species, direct electrochemical detection has been challenging. Herein, we report a stimuli-responsive polymer-based biosensor for His. The target receptors consist linear chain...
Voltage‐gated Ca 2+ ( V ) channels mediate ions influx into cells in response to depolarization of the plasma membrane. They are responsible for initiation excitation‐contraction and excitation‐secretion coupling, that enters through this pathway is also important regulation protein phosphorylation, gene transcription, many other intracellular events. Initial electrophysiological studies divided low‐voltage‐activated LVA high‐voltage‐activated HVA channels. The were further subdivided L, N,...
Psychiatric disorders are mental, behavioral or emotional disorders. These conditions prevalent, one in four adults suffer from any type of psychiatric world-wide. It has always been observed that have a genetic component, however new methods to sequence full genomes large cohorts identified with high precision risk loci for these conditions. include, but not limited to, bipolar disorder, schizophrenia, autism spectrum anxiety disorders, major depressive and attention-deficit hyperactivity...
The Ca V α 2 δ auxiliary subunit is a glycosylated protein that regulates the trafficking and function of voltage‐gated 2+ channels. One most prominent roles to increase whole‐cell current amplitude. Using N ‐glycosidase F truncated forms δ, earlier studies suggested an important role for ‐linked glycosylation in stimulation. Here, we used site‐directed mutagenesis heterologous expression HEK‐293 cells examine impact individual sites within on regulation Ba currents through recombinant We...
Abstract By mediating depolarization‐induced Ca 2+ influx, high‐voltage‐activated channels control a variety of cellular events. These heteromultimeric proteins are composed an ion‐conducting (α 1 ) and three auxiliary 2 δ, β γ) subunits. The α δ subunit enhances the trafficking channel complex to cell surface increases open probability. To exert these effects, must undergo important post‐translational modifications, including proteolytic cleavage that separates extracellular from its...
Auxiliary γ subunits are an important component of high-voltage-activated calcium (Ca V ) channels, but their precise regulatory role remains to be determined. In the current report, we have used complementary approaches including molecular biology and electrophysiology investigate influence on neuronal Ca channel activity expression. We found that coexpression 2 or 3 drastically inhibited macroscopic currents through recombinant N-type channels 2.2/β /α δ) in HEK-293 cells. Using inhibitors...
Abstract The majority of multiexon mammalian genes contain alternatively spliced exons that have unique expression patterns in different cell populations and important functions. profiles alternative are controlled by cell-specific splicing factors can promote exon inclusion or skipping but with few exceptions we do not know which specific control the known biological function. Many ion channel undergo extensive including Cacna1b encodes voltage-gated Ca V 2.2 α1 subunit. Alternatively 18a...
Glutamate (Glu) and histamine (His) are two major neurotransmitters that play many critical roles in brain physiological functions neurological disorders. Therefore, specific sensitive monitoring of Glu His is essential the diagnosis treatment various mental health neurodegenerative Both being non-electroactive species, direct electrochemical detection has been challenging. Herein, we report a stimuli-responsive polymer-based biosensor for His. The target receptors consist linear chain...
Glutamate (Glu) and histamine (His) are two major neurotransmitters that play many critical roles in brain physiological functions neurological disorders. Therefore, specific sensitive monitoring of Glu His is essential the diagnosis treatment various mental health neurodegenerative Both being non-electroactive species, direct electrochemical detection has been challenging. Herein, we report a stimuli-responsive polymer-based biosensor for His. The target receptors consist linear chain...