- Connexins and lens biology
- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Heat shock proteins research
- Nicotinic Acetylcholine Receptors Study
- Biochemical effects in animals
- Neuroscience and Neural Engineering
- Yersinia bacterium, plague, ectoparasites research
- Neural dynamics and brain function
- Lipid Membrane Structure and Behavior
- Caveolin-1 and cellular processes
- Hearing, Cochlea, Tinnitus, Genetics
- Muscle Physiology and Disorders
- Neurogenesis and neuroplasticity mechanisms
- Photoreceptor and optogenetics research
- Myasthenia Gravis and Thymoma
- Ion Transport and Channel Regulation
- Cardiomyopathy and Myosin Studies
- Barrier Structure and Function Studies
- Tissue Engineering and Regenerative Medicine
- RNA Research and Splicing
- Neurobiology and Insect Physiology Research
- Cellular transport and secretion
- Advanced Electron Microscopy Techniques and Applications
- Calpain Protease Function and Regulation
Colorado State University
2008-2018
Johns Hopkins University
1970-2003
University of Ottawa
2000
University of Manitoba
2000
In-Q-Tel
1999
GTx (United States)
1999
University of Maryland, Baltimore
1976-1982
University of Colorado Boulder
1974-1978
Jackson Laboratory
1974
Department of Embryology
1971-1974
Aquaporin (AQP) water channels are abundant in the brain and spinal cord, where AQP1 AQP4 believed to play major roles metabolism osmoregulation. Immunocytochemical analysis of recently revealed that has a highly polarized distribution, with marked expression astrocyte end-feet surround capillaries form glia limitans; however, structural organization remained unknown. In freeze-fracture replicas, contain square arrays intramembrane particles parallel distribution AQP4. To determine whether...
The transmembrane connexin proteins of gap junctions link extracellularly to form channels for cell-to-cell exchange ions and small molecules. Two primary hypotheses junction coupling in the CNS are following: (1) generalized occurs between neurons glia, with some connexins expressed both (2) intercellular junctional is restricted specific partners, different each cell type. There consensus that astrocytes oligodendrocytes, ependymocytes, other astrocytes. However, unresolved existence...
Osmotic homeostasis in the brain involves movement of water through aquaporin-4 (AQP4) membrane channels. Perivascular astrocyte end-feet contain distinctive orthogonal lattices (square arrays) assembled from 4- to 6-nm intramembrane particles (IMPs) corresponding individual AQP4 tetramers. Two isoforms result translation initiation at methionine residues M1 and M23, but no functional differences are known. In this study, Chinese hamster ovary cells were transfected with M1, or M1+M23...
Physiological and ultrastructural evidence indicates that gap junctions link many classes of neurons in mammalian central nervous system (CNS), allowing direct electrical metabolic communication. Among at least six junction-forming connexin proteins adult rat brain, connexin- (Cx) 32, Cx36, Cx43 have been reported to occur neurons. However, no has documented ultrastructurally defined neuronal junctions. To address this question directly, freeze-fracture replica immunogold labeling (FRIL)...
Mammalian fast and slow twitch skeletal muscles are compared by freeze-fracture, thick thin sectioning, histochemical techniques using conventional high voltage electron microscopy. Despite gross morphological differences in endplate structure visualized at relatively low magnifications this sections, rat extensor digitorum longus (EDL) (fast twitch) soleus (slow fibers cannot be distinguished on the basis of size, number, or distribution molecular specializations pre- postsynaptic...
The neuromuscular junctions and nonjunctional sarcolemmas of mammalian skeletal muscle fibers were studied by conventional thin-section electron microscopy freeze-fracture techniques. A modified acetylcholinesterase staining procedure that is compatible with light microscopy, techniques described. Freeze-fracture replicas utilized to visualize the internal macromolecular architecture nerve terminal membrane, chemically excitable junction postsynaptic folds, electrically sarcolemma. membrane...
Abstract The connexin family of proteins (Cx) that form intercellular gap junctions in vertebrates is well represented the mammalian central nervous system. Among these, Cx30 and Cx43 are present astrocytes. Cx32 expressed by oligodendrocytes heterologous between astrocytes as at autologous successive myelin layers. Cx36 mRNA has been identified neurons, protein localized ultrastructurally defined interneuronal junctions. Cx26 also CNS, primarily leptomeningeal linings, but reported neurons...
We have identified cells expressing Cx26, Cx30, Cx32, Cx36 and Cx43 in gap junctions of rat central nervous system (CNS) using confocal light microscopic immunocytochemistry freeze-fracture replica immunogold labeling (FRIL). Confocal microscopy was used to assess general distributions connexins, whereas the 100-fold higher resolution FRIL allowed co-localization several different connexins within individual ultrastructurally-defined junction plaques ultrastructurally immunologically cell...
Abstract Oligodendrocytes in vivo form heterologous gap junctions with astrocytes. These oligodendrocyte/astrocyte (A/O) contain multiple connexins (Cx), including Cx26, Cx30, and Cx43 on the astrocyte side, Cx32, Cx29, Cx47 oligodendrocyte side. We investigated connexin associations at A/O oligodendrocytes normal Cx32 knockout (KO) mice. Immunoblotting immunolabeling by several different antibodies indicated presence of liver brain mice, but absence KO confirming specificity efficacy...
The aquaporin-4 (AQP4) pool in the perivascular astrocyte membranes has been shown to be critically involved formation and dissolution of brain edema. Cerebral edema is a major cause morbidity mortality stroke. It therefore essential know whether AQP4 up- or down-regulated after an ischemic insult, because such changes would determine time course formation. Here we demonstrate by quantitative immunogold cytochemistry that striatum neocortex show distinct patterns expression reperfusion phase...
The inwardly rectifying K+ channel Kir4.1 is broadly expressed by CNS glia and deficits in lead to seizures myelin vacuolization. However, the role of oligodendrocyte channels controlling myelination clearance white matter has not been defined. Here, we show that selective deletion from progenitors (OPCs) or mature oligodendrocytes did impair their development disrupt structure myelin. mice lacking exhibited profound functional impairments, including slower extracellular delayed recovery...
Previously, synaptic activity in the spinal cord of adult mammals was attributed exclusively to chemical neurotransmission. In this study, evidence obtained for existence, relative abundance, and widespread distribution "mixed" (chemical electrical) synapses on neurons throughout cords mammals. Using combined confocal microscopy "grid-mapped freeze fracture," 36 mixed containing 88 "micro" gap junctions (median = 45 connexons) were found mapped 33 interneurons motor Rexed laminae III-IX...
In white matter regions of the brain and spinal cord adult mammals, gap junctions previously were observed linking astrocytes to astrocytes, as well oligodendrocytes ependymacytes. The resulting "functional syncytium" was proposed modulate ion fluxes that occur during electrical activity associated axons. Gap also have been reported neurons with glia, functional neuronal-glial coupling has postulated. To investigate glial syncytium neuron-to-glial hypotheses, we used "grid-mapped freeze...