Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “lateral fenestrations”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

11 recordsLinked to original sources
PubMed2024

Unplugging lateral fenestrations of NALCN reveals a hidden drug binding site within the pore region.

The sodium (Na+) leak channel (NALCN) is a member of the four-domain voltage-gated cation channel family that includes the prototypical voltage-gated sodium and calcium channels (NaVs and CaVs, respectively). Unlike NaVs and CaVs, which have four lateral fenestrations that serve as routes for lipophilic compounds to enter the central cavity to modulate channel function, NALCN has bulky residues (W311, L588, M1145, and Y1436) that block these openings. Structural data suggest that occluded fenestrations underlie the pharmacological resistance of NALCN, but functional evidence is lacking. To test this hypothesis, we unplugged the fenestrations of NALCN by substituting the four aforementioned residues with alanine (AAAA) and compared the effects of NaV, CaV, and NALCN blockers on both wild-type (WT) and AAAA channels. Most compounds behaved in a similar manner on both channels, but phenytoin and 2-aminoethoxydiphenyl borate (2-APB) elicited additional, distinct responses on AAAA channels. Further experiments using single alanine mutants revealed that phenytoin and 2-APB enter the inner cavity through distinct fenestrations, implying structural specificity to their modes of access. Using a combination of computational and functional approaches, we identified amino acid residues critical for 2-APB activity, supporting the existence of drug binding site(s) within the pore region. Intrigued by the activity of 2-APB and its analogues, we tested compounds containing the diphenylmethane/amine moiety on WT channels. We identified clinically used drugs that exhibited diverse activity, thus expanding the pharmacological toolbox for NALCN. While the low potencies of active compounds reiterate the pharmacological resistance of NALCN, our findings lay the foundation for rational drug design to develop NALCN modulators with refined properties.

Binding Sites↗
PubMed1979

Long-term effect of otosclerosis on bone conduction.

There have not been many studies of long-term sensorineural function in otosclerosis. The reports of long-term follow-up of lateral canal fenestration cases show a surprising stability of bone conduction. Because the experience of the senior author in stapes surgery suggests that some patients with clinically proven otosclerosis have a tendency for progression of sensorineural hearing loss, a review of over 500 ears in patients with proven otosclerosis was undertaken. Data from the study indicate that patients with otosclerosis have more sensorineural hearing loss than the general population. Also some otosclerotic ears have a tendency for progression of sensorineural hearing loss.

Audiometry↗
PubMed1977

Cephalometric observations in premature craniosynostosis.

Forty patients with premature craniosynostosis of variable extent and severity were subjected to cephalometry. The majority of the children and adolescents involved had undergone bilateral cranial fenestration at age 6 months to 11 years. Lateral cephalometric radiographs were used for analysis. The measurements obtained were compared with normal values of comparable age groups. In two thirds of the patients examined facial skull growth was found to be impaired, the clinical appearance ranging from pronounced faciostenosis to abortive forms. In some cases the clinical appearance was normal. One of the conclusions derived from the cephalometric data is that inhibited growth primarily affects the anterior portions of the skull base, which are found to be shorter than normal. The defect appears to involve the spheno-ethmoidal, intersphenoidal and sphenofrontal synochondroses.

Cephalometry↗
PubMed1978

Continuity between the ventricular and subarachnoid cerebrospinal fluid in an amphibian, Rana pipiens.

Continuity between the ventricular and subarachnoid cerebrospinal fluid has been investigated in Rana pipiens. The structure of the posterior tela, a deficient membrane situated at the extreme caudal end of the roof of the fourth ventricle, has been studied using whole membrane mounts and by light microscopy of resin embedded tissue. The ependymal component consists of columnar and rounded cells which form a regular 'syncytium' enclosing round and oval fenestrations. Small fenestrations are covered on the subarachnoid side by elongated pial cells and thus do not give total continuity between the fourth ventricle and the subarachnoid space. Large fenestrations, on the other hand, are accompanied by equivalent pial fenestrations giving direct access between the fluid compartments. Towards the caudal end the fenestrations break up and the numbers of ependymal and pial cells decrease, the caudal end itself being characterised by a small remaining clump of ependyma and pia or of pia alone. Flow through the tela has been studied using fluorescein-labelled dextran placed in the intraventricular space. Infusion into the lateral ventricle and subsequent localisation by fluorescence microscopy shows the marker to be in the fourth ventricle, in the fenestrations of the posterior tela and in the subarachnoid space overlying the tela. Infusion of the marker followed by freezing and examination of the cut heads on a freezing microtome, shows fluorescence throughout the ventricular system, in the subarachnoid space adjacent to the posterior tela and also along the dorsal subarachnoid space of the spinal cord.

Animals↗
PubMed1976

[Fine structure of human nasal mucosa in acute allergic reaction (author's transl)].

The fine structure of the acute allergic reaction is described in the human nasal mucosa. Subsequent to intranasal allergic testing with positive reaction characteristic changes are seen after different time intervals: Massive transudation into the dilated intercellular spaces, loss of epithelial junctions, extrusion of epithelial cells into the nasal lumen; increase permeability of capillaries and venules with increase of fenestrations and pinocytotic vesicles, edema of the cytoplasm and dilatation of intercellular junctions in the endothelium. Characteristic for the later stages are pronounced lesions of the vessel walls with interruption of cell junctions interstitial edema. endothelial gaps and loss of endothelial cells. The endothelial basal membrane usually remains intact. The findings are compared with those described for the acute hyperergic reaction in animals and chronic allergic changes in the human nasal mucosa.

Acute Disease↗
PubMed1979

Fine structure of the liver in the larval lamprey, Petromyzon marinus L.; hepatocytes and sinusoids.

The ultrastructure of hepatocytes, bile canaliculi, and hepatic sinusoids of the larval lamprey, Petromyzon marinus, was examined using thin-sectioned and freeze-fractured tissues. The liver is a "tubular gland" with hepatocytes arranged in a tubular fashion around large bile canaliculi. Hepatocytes are roughly conical in shape, with their tapered apices facing a bile canalicular lumen. They possess extensive rough and smooth endoplasmic reticulum, a well-developed Golgi complex, abundant mitochondria, and varying numbers of large secondary lysosomes. Both secondary lysosomes and the Golgi complex are concentrated in the apical or peribiliary cytoplasm, indicating a possible role in bile secretion. The apical surfaces of the hepatocytes bear numerous elongate microvilli and occasional cilia, which project into the bile canaliculi. The hepatocytes are joined, apically, by junctional complexes composed of zonulae occludentes and adhaerentes. In freeze-fracture, the zonulae occludentes are of variable apicobasal depth and consist of honeycomb-like meshworks of fibrils. Spaces of variable width frequently appear in the P-face grooves, indicating that the zonulae occludentes are "leaky." Numerous communicating (gap) junctions join the hepatocytes laterally. Varying numbers of lateral microvilli project into the intercellular spaces and, basally, the plasma membrane is deeply infolded, resulting in the formation of apparently interdigitating basal processes resting upon a thin basal lamina. Sinusoids are composed of both a heavily-fenestrated, continuous endothelium, and phagocytic reticulo-endothelial (Kupffer) cells. Depsite the difference in arrangement of their hepatocytes, the mammalian and lamprey livers show similar ultrastructural features.

Animals↗
PubMed1975

Golgi studies of the first optic ganglion of the ant, Cataglyphis bicolor.

The neurons of the first optic ganglion (the lamina) in the desert ant, Cataglyphis bicolor, have been studied with the light microscope after Golgi silver impregnation. The different types of retinal and laminal fibres and their configuration are compared with the results obtained in the bee. The first synaptic region in the visual system of the ant lies proximally to the fenestrated layer below the basement membrane and the layer containing the monopolar cell bodies. The synaptic region can be separated into three morphologically different zones: (1) The most distal layer where the short visual fibres end at two different levels. The short visual fibres and some laminal fibres (monopolar cell fibres) also show lateral elements in this region. (2) The second layer appears almost free of branches of retinal and laminal fibres. (3) The most proximal layer, which has a characteristically dense horizontal structure resulting from the lateral elements of long visual, centrifugal, monopolar and tangential fibres. Nine cell axons arising from each ommatidium leave the retina. Six of these are short visual fibres and end at two different levels in the lamina. Three different types of short visual fibres can be distinguished by their different terminal depths and lateral branching pattern. The remaining three fibres, the long visual fibres, terminate in the medulla. They can be distinguished from each other by their lateral elements in the lamina neuropile. The five morphologically different laminal fibre types (axons of the monopolar cells in the lamina) have different shapes and different arborizations at different levels. Tangential, centrifugal and incerta sedis-fibres, which originate either from cell bodies in the cell body layer at the periphery of the outer chiasma or more centrally, terminate in the synaptic region of the lamina. Consideration is given to the clearly demarkated arrangement and length of the branching pattern of retinal and laminal fibres at different levels of the synaptic region of the lamina. In addition, a hypothetical connectivity pattern is discussed.

Animals↗
PubMed1977

Ultrastructure of the feline area postrema.

The morphology of the feline area posterma (AP), a circumventricular organ, has been studied by scanning (SEM) and transmission electron microscopy (TEM). In SEM preparations the boundary of the AP was sharply delineated by the absence of kinocilia. Microvilli were numerous and seemed to be concentrated at the junction between ependymal cells, imparting a polygonal surface pattern superimposed on cell boundaries. Some cell processes were present on the AP surface, but no supra-ependymal cell bodies could be seen over the AP proper. In TEM preparations the AP was characterized by blood vessels with distinct perivascular spaces. These spaces contained fibroblasts and collagen, and were limited by basal laminae. Capillary endothelial cells were typically fenestrated and contained numerous pinocytotic vesicles. Bulbous ending of attenuated cellular processes terminated on the external basal laminae of AP vasculture. Some of these endings could be traced to the cells covering the ventricular surface of the AP. These cells demonstrated several features co-mon to ependymal cells which have been identified as tanycytes. The presence of small neurons frequently seen in groups of three or four confirm previous light microscopic studies. Synapses predominantly of the axodendritic variety were observed, and both dense cored and clear cored vesicles were present on the same ending. Myelinated and unmyelinated axons were a consistent finding in the AP with the former being more abundant in the lateral margins of the AP and in the region of the area subpostrema. The chemoreceptive function of the AP has been widely accepted; however, studies indicate that it is not possible to distinguish species possessing an emetic reflex on the basis of ultrastructural morphology. The possibility that the AP serves functions in addition to emetic chemoreception is considered.

Animals↗
PubMed1978

Mixed (chemical and electrical) synapses on frog spinal motoneurons.

Freeze-fracture replicas and ultrathin sections were used to characterize the gap junctions on the somata and large dendrites of frog motoneurons found earlier by Sonnhof et al. (1977). In freeze-fracture replicas one of the specific features of these relatively frequent gap junctions is the presence of circular regions of non-junctional membrane ("fenestrae") within areas of typical gap junction appearance displaying P-face particles or E-face pits. Such "fenestrated" gap junctions are mostly associated with membrane specializations indicative of the active zone of a chemical synapse (including vesicle attachment sites in non anaesthetized animals) to constitute mixed synapses. These findings could be verified in ultrathin sections, which revealed that the vesicles of the chemical component of the mixed synapses were spherical and agranular. Our results suggest that the mixed synapses are predominantly axo-somatic and axo-dendritic. The existence of dendro-dendritic gap junctions in the ventral horn region as described by Sotelo and Taxi (1970) was verified in ultrathin sections; they were rare, solely electrotonic in character, and probably represent the morphological basis for the VR-EPSP (Katz and Miledi, 1963; Kubota and Brookhart, 1963), i.e. electrotonic coupling between motoneurons of different spinal segments (Washizu, 1960). Electrotonic coupling can also be demonstrated between motoneurons and afferent fibers of the dorsal root and the lateral column. Electrotonic potentials recorded within motoneurons during electrical stimulation of dorsal root or lateral column precede the chemical postsynaptic potentials; after Mn2+-blockade of chemical synaptic transmission, the electrotonic component persists. Some fibers of these afferent pathways are therefore assumed to act monosynaptic on the motoneuron via mixed axo-somatic and axo-dendritic synapses.

Animals↗