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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exposure of cultured neonatal rat heart cells to simulated ischaemia results in a cessation of the spontaneous contractile activity and changes at both the level of sarcolemmal phospholipid topology and the ultrastructural level. Reperfusion at a timepoint before irreversible cell damage develops leads to a recovery of contractile activity. Furthermore, the shift in transbilayer distribution of sarcolemmal phosphatidylethanolamine in favour of the outer membrane leaflet, due to the ischaemic period, is reversed during subsequent reperfusion. Also the morphological changes (mitochondrial oedema, reorganization of the mitochondrial cristae and the formation of extrusions at the sarcolemma) are reversible. At the same time total intracellular ATP levels are restored to 80% of control. The role of cellular ATP content on sarcolemmal phospholipid topology was further studied by the use of the calcium antagonist verapamil (10 microM), which preserved cellular ATP content by inhibiting cell contractility before the onset of ischaemia. After 120 min of ischaemia, cell ATP content was still 63% of control in the presence of verapamil, versus 20% of control in untreated cells. Verapamil treatment also prevented the loss of the asymmetrical distribution of phosphatidylethanolamine and sarcolemmal disruption, the latter occurring during 120 min of ischaemia in untreated cells. It is proposed that maintenance of phospholipid asymmetry of the sarcolemma of the myocytes depends on the cellular ATP concentrations, indicating the involvement of an ATP dependent aminophospholipid translocase.
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PMID:Sarcolemmal phosphatidylethanolamine reorganization during simulated ischaemia and reperfusion: reversibility and ATP dependency. 890 44

The physicochemical properties of water enable it to act as a solvent for electrolytes, and to influence the molecular configuration and hence the function--enzymatic in particular--of polypeptide chains in biological systems. The association of water with electrolytes determines the osmotic regulation of cell volume and allows the establishment of the transmembrane ion concentration gradients that underlie nerve excitation and impulse conduction. Fluid in the central nervous system is distributed in the intracellular and extracellular spaces (ICS, ECS) of the brain parenchyma, the cerebrospinal fluid, and the vascular compartment--the brain capillaries and small arteries and veins. Regulated exchange of fluid between these various compartments occurs at the blood-brain barrier (BBB), and at the ventricular ependyma and choroid plexus, and, on the brain surface, at the pia mater. The normal BBB is relatively permeable to water, but considerably less so to ions, including the principal electrolytes Brain fluid regulation takes place within the context of systemic fluid volume control, which depends on the mutual interaction of osmo-, volume-, and pressure-receptors in the hypothalamus, heart and kidney, hormones such as vasopressin, renin-angiotensin, aldosterone, atriopeptins, and digitalis-like immunoreactive substance, and their respective sites of action. Evidence for specific transport capabilities of the cerebral capillary endothelium, for example high Na+K(+)-ATPase activity and the presence at the abluminal surface of a Na(+)--H+ antiporter, suggests that cerebral microvessels play a more active part in brain volume regulation and ion homoeostasis than do capillaries in other vascular beds. The normal brain ECS amounts to 12-19% of brain volume, and is markedly reduced in anoxia, ischaemia, metabolic poisoning, spreading depression, and conventional procedures for histological fixation. The asymmetrical distributions of Na+ K+ and Ca2+ between ICS and ECS underlie the roles of these cations in nerve excitation and conduction, and in signal transduction. The relatively large volume of the CSF, and extensive diffusional exchange of many substances between brain ECS and CSF, augment the ion-homeostasing capacity of the ECS. The choroid plexus, in addition to secreting CSF principally by biochemical mechanisms (there is an additional small component from the extracellular fluid), actively transports some substances from the blood (e.g. nucleotides and ascorbic acid), and actively removes others from the CSF. In contrast with CSF secretion, CSF reabsorption is principally a biomechanical process, passively dependent on the CSF-dural sinus pressure gradient. Pathological increases in intracranial water content imply development of an intracranial mass lesion. The additional water may be distributed diffusely within the brain parenchyma as brain oedema, as a cyst, or as increase in ventricular volume due to hydrocephalus. Brain oedema is classified on the basis of pathophysiology into four categories, vasogenic, cytotoxic, osmotic and hydrostatic. The clinical conditions in which brain oedema presents the greatest problems are tumour, ischaemia, and head injury. Peritumoural oedema is predominantly vasogenic and related to BBB dysfunction. Ischaemic oedema is initially cytotoxic, with a shift of Na+ and CI- ions from ECS to ICS, followed by osmotically obliged water, this shift can be detected by diffusion-weighted MRI. Later in the evolution of an ischaemic lesion the oedema becomes vasogenic, with disruption of the BBB. Recent imaging studies in patients with head injury suggest that the development of traumatic brain oedema may follow a biphasic time course similar to that of ischaemic oedema. Hydrocephalus is associated in the great majority of cases with an obstruction to the circulation or drainage of CSF, or, occasionally, with overproduction of CSF by a choroid plexus papilloma. In either case, the consequence is a ris
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PMID:The normal and pathological physiology of brain water. 907 71

Freeze-fracture electron microscopy was applied to study membrane morphology in a phosphatidylethanolamine-deficient E. coli strain. For growth, this strain requires millimolar concentrations of specific divalent cations like Mg2+ or Ca2+. These cations bring the bilayer to nonbilayer phase transition temperature of the lipids back to wild type levels by shifting the phase preference of cardiolipin in the membrane towards the inverted hexagonal (H(II)) phase. Under growth conditions, these cells show a bilayer based membrane with an intramembrane particle distribution as in wild type cells. Upon lowering the temperature, smooth areas are observed corresponding to gel state lipid bilayer domains. Ca2+ was used to manipulate the phase behavior of the membrane lipids in situ. Exposing the cells to Ca2+ up to 100 mM at 42 degrees C did not result in the appearance of nonbilayer structures, despite the fact that in total lipid extracts under these conditions the hexagonal H(II) phase was observed. However, the addition of a Ca2+ ionophore, which leads to exposure to Ca2+ of both faces of the plasma membrane, gives rise to formation of H(II) phase, stacked bilayer domains and blebbing upon addition of 50 mM CaCl2 at 42 degrees C. We conclude that the asymmetrical localization of divalent cations in the periplasm of this strain allows them to be functionally effective while membrane stability is maintained.
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PMID:A freeze-fracture study of the membrane morphology of phosphatidylethanolamine-deficient Escherichia coli cells. 909 13

The cellular and synaptic localization of immunoreactivity for the N-methyl-D-aspartate (NMDA) receptor subunit, NMDAR1, was investigated in inferotemporal and prefrontal association neocortices of monkeys and humans. In all monkey association areas examined, the laminar distribution patterns of NMDAR1 immunoreactivity were similar, and characterized by predominant pyramidal-like neuronal labeling in layers II, III, V and VI and a dense neuropil labeling consisting of intensely stained puncta and fine-caliber processes present throughout layers I-III, and V-VI. Layer IV, in contrast, contained only very lightly immunostained neurons which mostly lacked extensive dendritic staining. The laminar distribution of NMDAR1 immunolabeling in human association cortex was similar to that observed in monkeys. Electron microscopy of monkey areas 46 and TE1 confirmed that intensely immunoreactive asymmetrical postsynaptic densities were present throughout all cell-dense layers of prefrontal and inferotemporal association cortex. Quantitative analyses of the laminar proportions of immunoreactive synapses demonstrated that in both areas examined, the percentages of immunolabeled synapses were mostly similar across superficial layers, layer IV and infragranular layers. Finally, quantitative double-labeling immunofluorescence for non-NMDA receptor subunits or calcium-binding proteins demonstrated that virtually all GluR2/3 or GluR5/6/7-immunoreactive neurons were also labeled for NMDAR1, while regionally-specific subsets of parvalbumin-, calbindin- and calretinin-immunoreactive neurons were co-labeled. These data indicate that in primate association cortex, NMDA receptors are heterogeneously distributed to subsets of functionally distinct types of neurons and subsets of excitatory synapses, suggesting a critical and highly specific role in mediating the activity of excitatory connectivity which converges on cortical association areas.
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PMID:Quantitative localization of NMDAR1 receptor subunit immunoreactivity in inferotemporal and prefrontal association cortices of monkey and human. 913 25

Previous immunocytochemical studies in the cerebral cortex of various species have shown that the calcium-binding protein calretinin (CR) labels specific subpopulations of nonspiny nonpyramidal cells (interneurons). The present study attempts to characterize morphologically and chemically the microcircuitry of CR-immunoreactive (CR-ir) neurons in the human temporal neocortex. Postembedding immunocytochemistry for CR and GABA and combination immunocytochemistry for CR and nonphosphorylated neurofilament protein (NPNFP) or for CR and the calcium-binding proteins parvalbumin (PV) and calbindin (CB) showed CR multiterminal endings frequently innervating the distal apical dendrite or the cell body and proximal dendrites of NPNFP-ir or CB-ir pyramidal cells, respectively. Cell bodies of interneurons immunoreactive for CB or PV were innervated only occasionally by CR multiterminal endings, whereas certain GABA neurons were surrounded by them. Furthermore, CR-ir axon terminals formed either symmetrical (the majority) or asymmetrical synapses with a variety of postsynaptic elements. These results indicate that different subpopulations of CR interneurons exist that are specialized for selective innervation of somatic or dendritic regions of certain pyramidal and nonpyramidal neurons.
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PMID:Synaptic connections of calretinin-immunoreactive neurons in the human neocortex. 918 52

It is known that locally elevated Ca2+ at the growing tips of pollen tubes is necessary for pollen tube elongation. Here we show that this localized Ca2+ is also temporally regulated and is closely associated with pulsatile tip growth. Lilium longiflorum pollen tubes were injected with the photoprotein, aequorin, and the Ca2(+)-dependent light output was detected with a low noise photon-counting system. Ca2+ pulses with a mean period of 40 seconds were invariably associated with growth. The pulses were sporadic and of low amplitude for about the first 1.5 hours after germination. With subsequent growth, pulses increased in amplitude and the period between pulses became more regular. We have localized these Ca2+ pulses to the elongating end of the growing tube. The Ca2+ pulses are asymmetrical, rising more slowly than they fall. We estimate that the Ca2+ concentration at the peak of the pulses reaches nearly 10 microM. The addition of 100 microM La3+, a Ca2+ channel blocker, extinguished the pulses. An analysis of growth of elongating tubes establishes that extension is pulsatile, with a 42 second period between pulses. Calcium imaging, using the fluorescent indicator, Calcium Green dextran, shows that calcium pulses are coincident with peak growth rates.
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PMID:Tip localized Ca2+ pulses are coincident with peak pulsatile growth rates in pollen tubes of Lilium longiflorum. 920 87

In the cortical collecting duct of the rat two Ca(2+)-dependent K+ channels have been described so far. In the luminal membrane a maxi K+ channel with a single channel conductance of 139 +/- 3 pS in excised membrane patches (n = 91) at 0 mV clamp voltage and asymmetrical KCl-concentrations in pipette and bath was found, while in the basolateral membrane an intermediate conductance K+ channel (85 +/- 1 pS, n = 53) and a small K+ channel (28 +/- 2 pS, n = 15) was described. All these K+ channels had similar pharmacological properties since all could be blocked by the K+ channel inhibitors Ba2+, TEA+, and charybdotoxin. Verapamil, known as a L-type Ca2+ channel blocker, was also capable of inhibiting these K+ channels. While the maxi K+ channel from the luminal membrane was upregulated by intracellular Ca2+ (EC50: 5 microM), the small and the intermediate K+ channel from the basolateral membrane were downregulated (IC50: 10 microM). When the cytosolic Ca(2+)-activity was in the physiological range below 1 microM the activity of the maxi K+ channel was low and regulated via intracellular pH and ATP. Furthermore, when CCD cells were strongly depolarized and under hypoosmotic stress, Ca2+ rose and activated this K+ channel, indicating that this channel is involved in volume regulation. Like the maxi K+ channel the intermediate conductance K+ channel from the basolateral membrane was also sensitive to intracellular changes of pH where acidic pH inhibited while alkaline pH activated this channel. But unlike the K+ channels from the luminal membrane the K+ channel from the basolateral membrane is not regulated by ATP up to 5 mM. The activity of the K+ channels from the basolateral membrane decreased steadily after excision of the membrane. This decrease could be prevented by applying cGMP and MgATP to the bath and thus, activating a membrane-bound cGMP-dependent protein kinase (PKG). The activation of the PKG could be reversed by its specific inhibitor KT5823 (1 microM). Due to the opposite regulation via intracellular Ca2+ and the involvement of different protein kinases a specific and independent regulation of K+ secretion and Na+ reabsorption is possible in the CCD of the rat.
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PMID:Ca(2+)-dependent K+ channels in the cortical collecting duct of rat. 926 90

Previous studies have demonstrated formation of recurrent excitatory circuits between sprouted mossy fibers and granule cell dendrites in the inner molecular layer of the dentate gyrus (9, 28, 30). In addition, there is evidence that inhibitory nonprincipal cells also receive an input from sprouted mossy fibers (39). This study was undertaken to further characterize possible target cells for sprouted mossy fibers, using immunofluorescent staining for different calcium-binding proteins in combination with Timm histochemical staining for mossy fibers. Rats were injected intraperitoneally with kainic acid in order to induce epileptic convulsions and mossy fiber sprouting. After 2 months survival, hippocampal sections were immunostained for parvalbumin, calbindin D28k, or calretinin followed by Timm-staining. Under a fluorescent microscope, zinc-positive mossy fibers in epileptic rats were found to surround parvalbumin-containing neurons in the granule cell layer and to follow their dendrites, which extended toward the molecular layer. In addition, dendrites of calbindin D28k-containing cells were covered by multiple mossy fiber terminals in the inner molecular layer. However, the calretinin-containing cell bodies in the granule cell layer did not receive any contacts from the sprouted fibers. Electron microscopic analysis revealed that typical Timm-positive mossy fiber terminals established several asymmetrical synapses with the soma and dendrites of nonpyramidal cells within the granule cell layer. These results provide direct evidence that, in addition to recurrent excitatory connections, inhibitory circuitries, especially those responsible for the perisomatic feedback inhibition, are formed as a result of mossy fiber sprouting in experimental epilepsy.
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PMID:Characterization of target cells for aberrant mossy fiber collaterals in the dentate gyrus of epileptic rat. 927 41

1. Whole-cell and single-channel K+ currents were recorded at room temperature (22-24 degrees C), from smooth muscle cells enzymatically dispersed from the mouse ileum, using variations of the patch-clamp technique. 2. Net outward K+ currents recorded through amphotericin-B-perforated patches in response to step depolarizations positive to -50 mV from a holding potential of -80 mV were decreased by up to 70% by external apamin (0.5 microM). Apamin-sensitive whole-cell currents were also recorded from cells perfused internally with 150 nM Ca2+ but not from cells perfused internally with 85 nM Ca2+. 3. Three types of non-inactivating Ca(2+)-sensitive K+ channels were identified in cell-attached and excised patches under an asymmetrical K+ gradient: (i) large conductance (BKCa; approximately 200 pS) channels blocked by 2 mM external TEA; (ii) intermediate conductance (IKCa; approximately 39 pS) channels blocked by 2 mM external TEA and inhibited by external apamin (0.5 microM); and (iii) small conductance (SKCa; approximately 10 pS) channels that were not blocked by 5 mM external TEA but were sensitive to extracellular apamin (0.5 microM). 4. The TEA-resistant SKCa channels were activated by an increase in [Ca2+]i with an EC50 of 1.5 microM and a Hill coefficient of 1.3. 5. P2 purinoceptor agonists 2-methylthioATP (2-MeSATP), 2-chloroATP and ATP (10-50 microM) increased an apamin-sensitive whole-cell outward K+ current. Extrapatch application of 2-MeSATP (20-100 microM) stimulated the apamin-sensitive IKCa and SKCa channels and activated an apamin-sensitive steady outward current at 0 mV. 6. Smooth muscle cells from the mouse ileum possess two apamin-sensitive K+ channels (IKCa and SKCa); of these, the IKCa channels are TEA sensitive while the SKCa channels are TEA resistant. These channels, along with an apamin-sensitive but TEA-resistant steady outward current, may mediate membrane hyperpolarization elicited by purinergic agonists.
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PMID:Activation of small conductance Ca(2+)-dependent K+ channels by purinergic agonists in smooth muscle cells of the mouse ileum. 927 3

Current voltage (I-V) relations were measured from the calcium release channel (CRC) of the sarcoplasmic reticulum of cardiac muscle in 12 KCl solutions, symmetrical and asymmetrical, from 25 mM to 2 M. I-V curves are nearly linear, in the voltage range +/- 150 mV approximately 12kT/e, even in asymmetrical solutions, e.g., 2 M // 100 mM. It is awkward to describe straight lines as sums of exponentials in a wide range of solutions and potentials, and so traditional barrier models have difficulty fitting this data. Diffusion theories with constant fields predict curvilinear I-V relations, and so they are also unsatisfactory. The Poisson and Nernst-Planck equations (PNP) form a diffusion theory with variable fields. They fit the data by using adjustable parameters for the diffusion constant of each ion and for the effective density of fixed (i.e., permanent) charge P(x) along the channel's "filter" (7-A diameter, 10 A long). If P(x) is described by just one parameter, independent of x (i.e., P(x) = P0 = -4.2 M), the fits are satisfactory (RMS error/RMS current = 6.4/67), and the estimates of diffusion coefficients are reasonable D(K) = 1.3 x 10(-6) cm2/s, D(Cl) = 3.9 x 10(-6) cm2/s. The CRC seems to have a small selectivity filter with a very high density of permanent charge. This may be a design principle of channels specialized for large flux. The Appendix derives barrier models, and their prefactor, from diffusion theories (with variable fields) and argues that barrier models are poor descriptions of CRCs in particular and open channels in general.
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PMID:Permeation through the calcium release channel of cardiac muscle. 928 2


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