A5089069038- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Pain Mechanisms and Treatments
- Neurogenesis and neuroplasticity mechanisms
- Neuroscience and Neural Engineering
- Nerve injury and regeneration
- Nicotinic Acetylcholine Receptors Study
- Marine Toxins and Detection Methods
- Axon Guidance and Neuronal Signaling
- Functional Brain Connectivity Studies
- Lipid Membrane Structure and Behavior
- Neuropeptides and Animal Physiology
- Photoreceptor and optogenetics research
- Advanced Neuroimaging Techniques and Applications
- Hereditary Neurological Disorders
- Cardiac electrophysiology and arrhythmias
- Neurobiology and Insect Physiology Research
- Retinal Development and Disorders
- Nitric Oxide and Endothelin Effects
- Electrochemical Analysis and Applications
- Neural dynamics and brain function
- Botulinum Toxin and Related Neurological Disorders
- Muscle Physiology and Disorders
- Receptor Mechanisms and Signaling
- Electrochemical sensors and biosensors
Stanford University
2005-2024
University of California, Los Angeles
2018-2024
Palo Alto University
2022
University of Colorado Denver
2005-2020
University of Colorado Anschutz Medical Campus
1983-2020
Fitzsimons Army Medical Center
2008
University of Colorado Health
1998-2007
University of Colorado Hospital
1995-2002
Weizmann Institute of Science
2000
Stony Brook University
1997
Voltage-gated sodium channels perform critical roles for electrical signaling in the nervous system by generating action potentials axons and dendrites. At least 10 genes encode mammals, but specific physiological that distinguish each of these isoforms are not known. One possibility is isoform expressed a restricted set cell types or targeted to domain neuron muscle cell. Using affinity-purified isoform-specific antibodies, we find Na v 1.6 highly concentrated at nodes Ranvier both sensory...
Membrane excitability in different tissues is due, large part, to the selective expression of distinct genes encoding voltage-dependent sodium channel. Although predominant channels brain, skeletal muscle, and cardiac muscle have been identified, major channel types responsible for within peripheral nervous system remained elusive. We now describe deduced primary structure a channel, nerve type 1 (PN1), which expressed at high levels throughout targeted terminals cultured dorsal root...
Syntrophins are cytoplasmic peripheral membrane proteins of the dystrophin-associated protein complex (DAPC). Three syntrophin isoforms, alpha1, beta1, and beta2, encoded by distinct genes. Each contains two pleckstrin homology (PH) domains, a syntrophin-unique (SU) domain, PDZ domain. The name comes from first three found to contain repeats this domain (PSD-95, Drosophila discs large protein, zona occludens 1). domains in other bind C termini ion channels neurotransmitter receptors...
Voltage-dependent sodium channels cluster at high density axon initial segments, where propagating action potentials are thought to arise, and nodes of Ranvier. Here, we show that the channel Na(v)1.6 is precisely localized segments retinal ganglion cells (RGCs), whereas a different isoform, Na(v)1.2, found in neighboring unmyelinated axon. During development, first expressed appeared later, approximately parallel with onset repetitive RGC firing. In Shiverer mice, localization segment was...
Na(+) channel clustering at nodes of Ranvier in the developing rat optic nerve was analyzed to determine mechanisms localization, including possible requirement for glial contact vivo. Immunofluorescence labeling myelin-associated glycoprotein and protein Caspr, a component axoglial junctions, indicated that oligodendrocytes were present, paranodal structures formed, as early postnatal day 7 (P7). However, first clusters not seen until P9. Most these broad, all excluded from regions contact....
The K+ channel alpha-subunits Kv1.1 and Kv1.2 the cytoplasmic beta-subunit Kvbeta2 were detected by immunofluorescence microscopy found to be colocalized at juxtaparanodes in normal adult rat sciatic nerve. After demyelination intraneural injection of lysolecithin, during remyelination, subcellular distributions Kv1.1, Kv1.2, reorganized. At 6 d postinjection (dpi), axons stripped myelin, channels dispersed across zones that extended into both nodal internodal regions; a few days later they...
The tetrodotoxin-binding component associated with the voltage-sensitive sodium channel from electroplax membranes of Electrophorus electricus has been purified. toxin-binding site could be efficiently solubilized Lubrol-PX, resulting in an extract high initial specific activity. Purification was facilitated by development a rapid, quantitative binding assay. stabilized during purification use mixed lipid/detergent micelles defined composition, and saturation tetrodotoxin. achieved means...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPrincipal glycopeptide of the tetrodotoxin/saxitoxin binding protein from Electrophorus electricus: isolation and partial chemical physical characterizationJames A. Miller, William S. Agnew, Simon R. LevinsonCite this: Biochemistry 1983, 22, 2, 462–470Publication Date (Print):January 18, 1983Publication History Published online1 May 2002Published inissue 18 January...
Tenascin-R (TN-R), an extracellular matrix glycoprotein of the CNS, localizes to nodes Ranvier and perineuronal nets interacts in vitro with other components recognition molecules immunoglobulin superfamily. To characterize functional roles TN-R vivo , we have generated mice deficient for by homologous recombination using embryonic stem cells. TN-R-deficient are viable fertile. The anatomy all major brain areas formation structure myelin appear normal. However, immunostaining chondroitin...
The TTX‐sensitive Na v 1.7 (PN1) + channel α subunit protein is expressed mainly in small dorsal root ganglion (DRG) neurones. This study examines immunocytochemically whether it exclusively or preferentially nociceptive primary afferent DRG neurones, and determines the electrophysiological properties of neurones that express it. Intracellular somatic action potentials (APs) evoked by stimulation were recorded L6/S1 at 30 ± 2 °C vivo deeply anaesthetised young guinea‐pigs. Each neurone was...
The distribution and function of Shaker-related K + channels were studied with immunofluorescence electrophysiology in sciatic nerves developing rats. At nodes Ranvier, Na channel clustering occurred very early (postnatal days 1–3). Although not yet segregated at most these sites, they directly involved action potential generation, reducing duration, the refractory period. ∼1 week, clusters first seen but within nodal gap paranodes, only later (weeks 2–4) shifted to juxtaparanodal regions....
A potential role for sialic acid in the voltage-dependent gating of rat skeletal muscle sodium channels (rSkM1) was investigated using Chinese hamster ovary (CHO) cells stably transfected with rSkM1. Changes voltage dependence channel were observed after enzymatic (neuraminidase) removal from expressing rSkM1 and through expression a sialylation-deficient cell line (lec2). The steady-state half-activation voltages (Va) under each condition reduced sialylation ∼10 mV more depolarized than...
The node of Ranvier is a distinct domain myelinated axons that highly enriched in sodium channels and critical for impulse propagation. During development, the channel subtypes expressed at undergo transition from Na<sub>v</sub>1.2 to Na<sub>v</sub>1.6. Specialized junctions form between paranodal glial membranes axon flank nodes are candidates regulate their maturation delineate boundaries. To investigate these roles, we characterized development mice deficient contactin-associated protein...
The distribution of Na+ channels in rat peripheral nerve was measured during development by using immunofluorescence. Small segments sciatic from postnatal day 0-13 (P0-P13) pups were labeled with an antibody raised against a well conserved region the vertebrate channel. At P0 axons contained almost no channel aggregates. number clusters increased dramatically throughout first week. In all cases clustered vicinity Schwann cell processes. least four classes aggregates noted. Clusters formed...
Na + channel recovery from inactivation limits the maximal rate of neuronal firing. However, properties presynaptic channels are not well established because small size most CNS boutons. Here we study currents rat calyx Held terminal and compare them with those postsynaptic cells. We find that recover a fast, single-exponential time constant (24°C, τ 1.4-1.8 ms; 35°C, 0.5 ms), their accelerates twofold during development, which may contribute to shortening action potential as matures. In...
The congenital disorders of glycosylation (CDGs) are recent additions to the repertoire inherited human genetic diseases. Frequency CDGs is unknown since most cases believed be misdiagnosed or unrecognized. With few patients identified and heterogeneity in disease signs noted, studies animal models may provide increased understanding pathogenic mechanisms. However, features mammalian glycan biosynthesis species-specific variations repertoires have cast doubt on whether defects protein will...
Sodium channel (NaCh) expressions change following nerve and inflammatory lesions this may contribute to the activation of pain pathways. In a previous study we found dramatic increase in size density NaCh accumulations, remodeling NaChs at intact altered myelinated sites location just proximal combined partial axotomy chromic suture lesion rat infraorbital (ION) with use an antibody that identifies all isoforms. Here evaluate contribution major nodal isoform, Nav1.6, same lesion. Sections...