bluuebunny/crossref_metadata_2025 huggingface dataset:
An In Vitro Model of the Kitten Retinogeniculate Pathway
Authors: Guido William , Lo Fu-Sun , Erzurumlu Reha S.
Published: December 2017

Guido, William, Fu-Sun Lo, and Reha S. Erzurumlu. An in vitro model of the kitten retinogeniculate pathway. J. Neurophysiol. 77: 511–516, 1997. An organotypic explant coculture method is described for the developing retinogeniculate pathway of the cat. Retinal explants and thalamic slices containing the dorsal lateral geniculate nucleus (LGN), derived from early postnatal kittens, can be grown in serum-free culture medium for several days. In such cultures, retinal ganglion cells (RGCs) and LGN neurons retained their age-specific morphological features and developed functional connections. Labeling of RGCs and their processes with DiI showed that all three major classes of RGCs (α/Y, β/X, γ/W) were present in cocultured retinal explants. Retinal axons readily regenerated into thalamic slices and, over time, developed arbors within the LGN. Retrograde labeling from the LGN traced the origin of these axons almost exclusively to α-cells in the retina. In vitro intracellular recordings indicated that LGN cells maintained their basic electrophysiological properties in coculture. Current injection generated action potentials, and, at hyperpolarized levels, it led to low-threshold Ca2+ spiking. Regenerated retinal axons also formed functional connections with LGN neurons. Electrical stimulation of the retinal explant elicited excitatory postsynaptic responses (EPSPs) in LGN cells. Drop application of specific glutamate antagonists indicated that EPSPs had both N-methyl-d-aspartate (NMDA) and non-NMDA receptor components. The morphology of the LGN neurons was examined after intracellular injections of biocytin during recording. Labeled cells were very similar to those of early postnatal kittens. Although, in general, they had relatively small soma and simple dendritic branching patterns, a few could be recognized as X- or Y-cells. Thus the coculture model can be used to assay the regenerative propensity of different types of RGCs during development.
Detection of a Membrane Shunt by DC Field Polarization During Intracellular and Whole Cell Recording
Authors: Svirskis Gytis , Gutman Aron , Hounsgaard Jørn
Published: December 2017

Svirskis, Gytis, Aron Gutman, and Jørn Hounsgaard. Detection of a membrane shunt by DC field polarization during intracellular and whole cell recording. J. Neurophysiol. 77: 579–586, 1997. Lower input resistance with intracellular recording, rather than with whole cell recording, usually has been ascribed to a shunt produced by penetration injury. An alternative explanation is a higher input resistance during whole cell recording due to wash-out of cytoplasmatic substances. We have used neuronal polarization at the onset and termination of an applied electric field for shunt detection. An analytical expression was derived for field-induced polarization in a shunted ohmic cable. When the shunt is negligible, the transient response to a step in DC field decays much faster than the response to current injected through the recording electrode. In the case of a significant shunt an over- and undershoot of the transmembrane potential appear at the shunted end when the field is switched on and off. Over- and undershoot decay with the same slowest time constant as the response to injected current. The results for the cable are generalized for nonuniform fields and arbitrary branching neurons with homogeneous membrane. The field effect was calculated for two reconstructed neurons with different branching pattern. The calculations confirmed the theoretical inferences. The field polarization can be used for shunt detection. The theory was checked experimentally in 18 ventral neurons in transverse slices of the turtle spinal cord. In seven neurons, field-induced under- and overshoots were observed when sharp electrodes were used. This indicates the presence of an injury shunt. In the remaining 11 neurons, however, there were no under- or overshoots, indicating that a shunt is not always induced. When patch electrodes were used, the seal quality was checked by inducing a spike with a strong field stimulus before and after the rupture of the membrane. When the threshold field strength for spike initiation was not changed by membrane rupture, under- and overshoots were not observed. This was taken to indicate a good seal. In such recordings under- and overshoots were observed when a shunt was induced by local application of glycine. The fast and monotonic response to weak field stimulation suggests homogeneous electric properties of the soma-dendritic membrane when active conductances are not recruited. We propose using polarization by weak DC fields to ensure the quality of recordings with sharp and whole cell electrodes and for checking the ohmic homogeneity of the membrane. These controls are particularly important for evaluation of electrotonic parameters.
Mechanisms Underlying the Enhancement of Excitatory Synaptic Transmission in Basolateral Amygdala Neurons of the Kindling Rat
Authors: Shoji Y. , Tanaka E. , Yamamoto S. , Maeda H. , Higashi H.
Published: December 2017

Shoji, Y., E. Tanaka, S. Yamamoto, H. Maeda, and H. Higashi. Mechanisms underlying the enhancement of excitatory synaptic transmission in basolateral amygdala neurons of the kindling rat. J. Neurophysiol. 80: 638–646, 1998. To elucidate the mechanism underlying epileptiform discharges in kindled rats, synaptic responses in kindled basolateral amygdala neurons in vitro were compared with those from control rats by using intracellular and whole cell patch-clamp recordings. In kindled neurons, electrical stimulation of the stria terminalis induced epileptiform discharges. The resting potential, apparent input resistance, current-voltage relationship of the membrane, and the threshold, amplitude, and duration of action potentials in kindled neurons were not different from those in control neurons. The electrical stimulation of stria terminalis elicited excitatory postsynaptic potentials (EPSPs) and dl-2-amino-5-phosphonopentanoic acid (AP5)-sensitive and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)-sensitive excitatory postsynaptic currents (EPSCs). The amplitude of evoked EPSPs and of evoked AP5-sensitive and CNQX-sensitive EPSCs were enhanced markedly, whereas fast and slow inhibitory postsynaptic potentials (IPSPs) induced by electrical stimulation of lateral amygdaloid nucleus were not significantly different. The rise time and the decay time constant of the evoked CNQX-sensitive EPSCs were shortened, whereas the rise time of the evoked AP5-sensitive EPSCs was shortened, but the decay time constants were not significantly different. In both tetrodotoxin (TTX)-containing medium and low Ca2+ and TTX-containing medium, the frequency and amplitude of spontaneous EPSCs were increased in kindled neurons. These increases are presumably due to nearly synchronous multiquantal events resulted from the increased probability of Glu release at the nerve terminals. The rise time of evoked CNQX- and AP5-sensitive EPSCs and the decay time constant of evoked CNQX-sensitive EPSCs were shortened, suggesting that excitatory synapses at the proximal dendrite and/or the soma in kindled neurons may contribute more effectively to generate evoked EPSCs than those at distal dendrites. In conclusion, the increases in the amplitudes of spontaneous and evoked EPSCs and in the frequency of spontaneous EPSCs may contribute to the epileptiform discharges in kindled neurons.
Physiological Survey of Medullary Raphe and Magnocellular Reticular Neurons in the Anesthetized Rat
Authors: Leung Cynthia G. , Mason Peggy
Published: December 2017

Leung, Cynthia G. and Peggy Mason. Physiological survey of medullary raphe and magnocellular reticular neurons in the anesthetized rat. J. Neurophysiol. 80: 1630–1646, 1998. The present study was designed to provide a detailed and quantitative description of the physiological characteristics of neurons in the medullary raphe magnus (RM) and adjacent nucleus reticularis magnocellularis (NRMC) under anesthetized conditions. The background discharge and noxious stimulus-evoked responses of RM and NRMC neurons were recorded in rats lightly anesthetized with isoflurane. All cells that were isolated successfully were studied. After recording background discharge, the neuronal response to repeated noxious thermal and noxious mechanical stimulation of the tail was recorded. Most cells were identified as nonserotonergic by their irregular or rapid background discharge pattern. Because the spontaneous discharge of most RM nonserotonergic cells contained pauses and bursts, a comparison between the change in rate evoked by tail heat and the range of rate changes that occur spontaneously was used to classify cells. The mean responses of on and off cells were more than four times the standard deviation of the changes in rate observed spontaneously. on cells were excited in 86% of the tail heat trials tested. Similarly, off cells were inhibited in 97% of the noxious tail heat trials tested. The heat-evoked changes in on and off cell discharge varied over more than two orders of magnitude and were greater in cells with greater rates of background discharge. The heat-evoked responses of on and off cells had durations of tens of seconds to minutes and were always sustained beyond the visible motor response. Most on and off cells responded to noxious tail clamp in a manner that was similar to their response to noxious heat. More than half of the neutral cells that were unresponsive to noxious heat were responsive to noxious tail clamp. A minority of on, off, and neutral cells responded to innocuous brush stimulation with weak, transient responses. Although many cells discharged too infrequently to be classified, units with physiological properties that were different from those described above were rare. In conclusion, most RM and NRMC cells belong to three nonserotonergic physiological cell classes that can be distinguished from each other by the consistency, not the magnitude, of their responses to repeated noxious thermal stimulation. Because most of the heat-evoked change in on and off cell discharge occurs after the conclusion of the initial motor withdrawal, on and off cells are likely to principally modulate the response to subsequent noxious insults.
Voltage-Dependent Uptake Is a Major Determinant of Glutamate Concentration at the Cone Synapse: An Analytical Study
Authors: Roska Botond , Gaal Lubor , Werblin Frank S.
Published: December 2017

Roska, Botond, Lubor Gaal, and Frank S. Werblin. Voltage-dependent uptake is a major determinant of glutamate concentration at the cone synapse: an analytical study. J. Neurophysiol. 80: 1951–1960, 1998. It was suggested that glutamate concentration at the synaptic terminal of the cones was controlled primarily by a voltage-dependent glutamate transporter and that diffusion played a less important role. The conclusion was based on the observation that the rate of glutamate concentration during the hyperpolarizing light response was dramatically slowed when the transporter was blocked with dihydrokainate although diffusion remained intact. To test the validity of this notion we constructed a model in which the balance among uptake, diffusion, and release determined the flow of glutamate into and out of the synaptic cleft. The control of glutamate concentration was assumed here to be determined by two relationships; 1) glutamate concentration is the integral over the synaptic volume of the rates of release, uptake, and diffusion, and 2) membrane potential is the integral over the membrane capacitance of the dark, leak, and transporter-gated chloride current. These relationships are interdependent because glutamate uptake via the transporter is voltage dependent and because the transporter-gated current is concentration dependent. The voltage and concentration dependence of release and uptake, as well as the light-elicited, transporter-gated, and leak currents were measured in other studies. All of these measurements were incorporated into our predictive model of glutamate uptake. Our results show a good quantitative fit between the predicted and the measured magnitudes and rates of change of glutamate concentration, derived from the two interdependent relationships. This close fit supports the validity of these two relationships as descriptors of the mechanisms underlying the control of glutamate concentration, it verifies the accuracy of the experimental data from which the functions used in these relationships were derived, and it lends further support to the notion that glutamate concentration is controlled primarily by uptake at the transporter.
Group I Metabotropic Glutamate Receptors Mediate Slow Inhibition of Calcium Current in Neocortical Neurons
Authors: Sayer Rod J.
Published: December 2017

Sayer, Rod J. Group I metabotropic glutamate receptors mediate slow inhibition of calcium current in neocortical neurons J. Neurophysiol. 80: 1981–1988, 1998. Metabotropic glutamate receptor (mGluR)-mediated inhibition of high-voltage-activated Ca2+ currents was investigated in pyramidal neurons acutely isolated from rat dorsal frontoparietal neocortex. Whole cell recordings were made at 30–32°C, with Ca2+ as the charge carrier. Selective agonists were used to classify the subgroup of mGluRs mediating the response. Ca2+ currents were inhibited by (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) and by the group I agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) but not by the group II agonist (2S,2′R,3′R)-2-(2′,3′-dicarboxycyclopropyl)glycine (DCG-IV) or the group III agonist l(+)-2-amino-4-phosphonobutryic acid (l-AP4). (2S,1′S,2′S)-2-(carboxycyclopropyl)glycine (l-CCG-I) was effective at 10 and 100 μM but not at 1 μM, consistent with involvement of group I mGluRs. Variable results were obtained with the putative mGluR5-selective agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG) and the putative mGluR1-selective antagonist (S)-4-carboxyphenylglycine [(S)-4CPG], indicating that the group I mGluR subtypes may vary between cells or that these compounds were activating other receptors. The actions of (+)-α-methyl-4-carboxyphenylglycine [(+)-MCPG] were consistent with it being a low-potency antagonist. Several features of the Ca2+ current inhibition evoked by DHPG distinguished it from the rapid modulation typical of a direct action of G proteins on Ca2+ channels; the inhibition was slow to reach maximum (tens of seconds), current activation was not slowed or shifted in the positive voltage direction, and the inhibition was not relieved by positive prepulses. Nimodipine and ω-conotoxin GVIA blocked fractions of the current and also reduced the magnitude of the responses to DHPG, indicating that both L- and N-type Ca2+ channels were regulated. These results further differentiate the slow modulatory pathway observed in neocortical neurons when Ca2+ is used as the charge carrier from the rapid voltage-dependent mechanism reported to inhibit Ba2+ currents under Ca2+-free conditions.
Molecular genetics of chromosome translocations involvingEWSand related family members
Authors: KIM JUNGHO , PELLETIER JERRY
Published: December 2017

Kim, Jungho, and Jerry Pelletier. Molecular genetics of chromosome translocations involving EWS and related family members. Physiol. Genomics 1: 127–138, 1999.—Many types of sarcomas are characterized by specific chromosomal translocations that appear to result in the production of novel, tumor-specific chimeric transcription factors. Many of these show striking similarities: the emerging picture is that the amino-terminal domain of the fusion product is donated by the Ewing's sarcoma gene ( EWS) or a related member from the same gene family, whereas the carboxy-terminal domain often consists of a DNA-binding domain derived from one of a number of transcription factors. Given the observation that the different translocation partners of the EWS protooncogene are associated with distinct types of sarcomas, the functional consequence of fusing EWS (or a related family member) to a different DNA-binding domain can only be understood in the context of functional studies that define the specificity of action of the different fusion products. An understanding of the molecular structure and function of these translocations provides new methods for diagnosis and novel targets for therapeutics.
Regulation of Angiotensin Receptors
Authors: Douglas JG
Published: December 2017

Angiotensin affects cardiovascular function through contraction of vascular smooth muscle and stimulation of aldosterone secretion, responses that are modulated by alterations in sodium or potassium balance. Changes in angiotensin receptor density of the target tissues are the major determinant of tissue responsiveness during alterations in electrolyte balance.
Starvation as a Treatment of Obesity: The Need to Conserve Body Protein
Authors: Le Maho Y , Robin J-P , Cherel Y
Published: December 2017

Starvation has successfully been used to treat severe human obesity but may be dangerous due to excessive loss of body protein. Obese humans when starving use fat and spare protein as effectively as those animals that spontaneously undergo prolonged fasting after accumulating large fat reserves. Nevertheless, slow loss of protein during complete starvation may in severely obese persons lead to a cumulative protein loss that leads to sudden death before the fat reserves are depleted.
The Physiology of the Liposome
Authors: Gregoriadis G
Published: December 2017

Understanding of the behavior and control of liposomes in vivo has led to their successful use as a drug delivery system in the treatment or prevention of a wide spectrum of diseases in experimental animals and, more recently, in clinical trials.
Successful Training of Biological Scientists in Developing Countries
Authors: Robertshaw David
Published: December 2017

Moroccan Physiologists are more likely to sustain their research Productivity when they return home after US doctoral training because of the program that has been carried out at the Institut Agronomique et Veterinaire in Rabat, Morocco, and funded by the US Agency for International Development.
Communication Among Endothelial and Smooth Muscle Cells Coordinates Blood Flow Control During Exercise
Authors: Segal SS
Published: December 2017

Peripheral blood flow control during exercise is coordinated among several vascular locations. The locus of control shifts upstream from distal arterioles into feeding arteries as metabolic demand increases. This shift occurs by cell-to-cell conduction and by flow-dependent endothelial cell-mediated relaxation of smooth muscle cells.
How the Lamprey Swims
Authors: Williams T , Sigvardt K
Published: December 2017

The goal of current research on locomotion in the lamprey is to obtain a complete neural and mechanical description of swimming in this species as a model for studies of motor control in vertebrates.
Angiotensin II Enhances Lipid Peroxidation of Low-Density Lipoprotein
Authors: Keidar S , Brook JG , Aviram M
Published: December 2017

Hypertensive patients demonstrate accelerated atherosclerosis, and angiotensin II has been suggested to play an important role in this phenomenon. Data are presented on the stimulatory effects of angiotensin II on the production of oxidized low-density lipoprotein and on macrophage foam cell formation.
Reactive Oxygen and Nitric Oxide in Skeletal Muscle
Authors: Reid MB
Published: December 2017

Skeletal muscle produces oxygen radicals, nitric oxide, and a variety of redox-active derivatives that modulate muscle function under physiological conditions. In unfatigued muscle, reactive oxygen intermediates and nitric oxide exert opposing effects on excitation-contraction coupling. During strenuous exercise, oxidants accumulate in the tissue and accelerate the fatigue process.
Functional Role of Pi Transport in Osteogenic Cells
Authors: Caverzasio J , Montessuit C , Bonjour J-P
Published: December 2017

Vesicles released into the bone matrix by growth plate chondrocytes and osteoblasts are considered important organelles for the development of primary calcification of bone. The Pi transport system in these structures plays an essential role in initial events responsible for accumulation of Ca2+ and Pi and calcification of these structures.
The Mammalian Muscle Spindle
Authors: Proske U
Published: December 2017

A brief, summarizing description is given of the structure and physiology of the mammalian muscle spindle. The question is addressed, What might be the roles of the three different kinds of intrafusal fibers on which the sensory endings lie? The role of muscle spindles in proprioception and in motor control is discussed.
Ethanol: Novel Actions on Nerve Cell Physiology Explain Impaired Functions
Authors: Korpi Esa R. , Mäkelä Riikka , Uusi-Oukari Mikko
Published: December 2017

Molecular biological tools have revealed receptor proteins for excitatory and inhibitory neurotransmitters on cell membranes as targets of ethanol action. Behavioral and pharmacogenetic assays using rodent lines have supported this neurotransmitter theory of ethanol action and given a firm basis for future identification of the relevant genes and the central physiological processes vulnerable to ethanol.
Humoral Regulation of Sleep
Authors: Krueger James M. , Fang Jidong , Hansen Michael K. , Zhang Jianyi , Obál Ferenc
Published: December 2017

Cytokines and hormones, including interleukin-1, tumor necrosis factor, growth hormone-releasing hormone, vasoactive intestinal polypeptide and prolactin, are involved in sleep regulation. These substances enhance sleep, inhibition of them inhibits sleep, and their brain levels vary with sleep. This knowledge helps our understanding of the humoral regulation of sleep.
Chemosensory Perception in the Gut
Authors: Höfer Dirk , Asan Esther , Drenckhahn Detlev
Published: December 2017

The ability of the gut mucosa to sense the chemical composition of chyme is important for gastrointestinal functions. The demonstration of gustducin and transducin, two α-subunits of GTP-binding proteins involved in gustatory signal transduction, in gastrointestinal epithelial cells provides first clues to the molecular basis of enteric chemosensitivity. Nitric oxide may play a role as a secondary messenger.
Astrocytes Couple Synaptic Activity to Glucose Utilization in the Brain
Authors: Magistretti Pierre J. , Pellerin Luc
Published: December 2017

Astrocytes have functional characteristics that make them particularly well suited to couple glutamate uptake from the synaptic cleft to Na+-K+-ATPase activation and glucose utilization. The changes in glucose metabolism associated with these processes may provide signals detected by positron emission tomography.
Extracellular Surface Charges in Voltage-Gated Ion Channels
Authors: Madeja Michael
Published: December 2017

A large number of charged amino acids are in the extracellularly located parts of the voltage-gated ion channels. Recent findings suggest that these surface charges contribute to the channel functions in the sensing of voltage, the binding of substances, and the sensing of H+ concentration.
Phospholipase C Isoforms, Cytoskeletal Organization, and Vascular Smooth Muscle Differentiation
Authors: Lymn Joanne S. , Hughes Alun D.
Published: December 2017

The function of differentiated vascular smooth muscle cells (VSMC) in vivo is the regulation of contractility. Following injury or disease, however, VSMC lose their contractile function and take on a synthetic, proliferative phenotype. This dedifferentiation is generally accompanied by a change in the expression profile of phospholipase C isoforms.
Mechanics of Relaxation of the Human Heart
Authors: Chemla Denis , Coirault Catherine , Hébert Jean-Louis , Lecarpentier Yves
Published: December 2017

Rapid and complete relaxation is a prerequisite for cardiac output adaptation to changes in loading conditions, inotropic stimulation, and heart rate. In the healthy human heart, the rate and extent of relaxation depend mainly on actomyosin cross bridge dissociation and on left ventricular end-systolic volume, rather than on the afterload level.
Calmodulin and Excitation-Contraction Coupling
Authors: Hamilton Susan L. , Serysheva Irina , Strasburg Gale M.
Published: December 2017

Excitation-contraction coupling in cardiac and skeletal muscle involves the transverse-tubule voltage-dependent Ca2+ channel and the sarcoplasmic reticulum Ca2+ release channel. Both of these ion channels bind and are modulated by calmodulin in both its Ca2+-bound and Ca2+-free forms. Calmodulin is, therefore, potentially an important regulator of excitation-contraction coupling. Its precise role, however, has not yet been defined.
Traffic Control: Rab GTPases and the Regulation of Interorganellar Transport
Authors: Tuvim Michael J. , Adachi Roberto , Hoffenberg Simon , Dickey Burton F.
Published: December 2017

Membrane proteins, membrane lipids, and luminal contents are exchanged among the intracellular compartments of eukaryotic cells by vesicular transport. This process must be highly ordered to maintain cellular architecture in the face of rapid membrane turnover. The Ras-related Rab GTPases play multiple roles in regulating this traffic.
Smooth Muscle Excitation-Contraction Coupling: a Role for Caveolae and Caveolins?
Authors: Taggart Michael J.
Published: December 2017

Agonist stimulation of smooth muscle contractility involves integration of many signal-transducing events from the plasma membrane to myofilaments in the cytoplasm. Recent evidence suggests an important role for membranous invaginations termed caveolae, and their integral protein components caveolins, in the coordination of extracellular contractile stimuli and intracellular effectors in smooth muscle.
Pleiotropic Functions and Tissue-Specific Expression of Erythropoietin
Authors: Sasaki Ryuzo , Masuda Seiji , Nagao Masaya
Published: December 2017

Erythropoietin (EPO) is produced in the brain, uterus, and oviduct. Brain EPO plays a neuroprotective role, and uterine EPO is likely involved in estrogen-dependent angiogenesis. Hypoxic induction of brain EPO markedly differs from that in the kidney. EPO in the uterus and oviduct is estrogen inducible.
Of Slow Waves and Spike Patches
Authors: Lammers Wim J. E. P. , Slack John R.
Published: December 2017

In the small intestines, the major task of the slow wave is to induce mechanical movements in the intestinal wall by generating local calcium spikes. High resolution electrical mapping reveals fundamental differences in propagation between slow waves and calcium spikes. These differences suggest that slow waves and spikes are propagated by different mechanisms through different cell networks.
Possible Genomic Consequence of Nongenomic Action of Glucocorticoids in Neural Cells
Authors: Chen Yi-Zhang , Qiu Jian
Published: December 2017

The nongenomic, rapid effects of glucocorticoid activate multiple intracellular transduction pathways. This review proposes a possible genomic consequence of the nongenomic action of steroids. The genomic actions of hormonal steroids may be twofold: classic genomic and nongenomically induced genomic.
Transport of molecules across renal glomerular capillaries
Authors: Brenner B. M. , Baylis C. , Deen W. M.
Published: December 2017

Direct measurements of the pressures and flows governing the formation of glomerular ultrafiltrate have been made possible in recent years by virtue of 1) the discovery of rats and monkeys possessing glomerular capillaries on the renal cortical surface, accessible to micropuncture, and 2) technological advances that permit measurement of intracapillary hydraulic pressure and assessment of the change in colloid osmotic pressure along the glomerular capillary network. Based on these direct measurements, evidence has been obtained to indicate that glomerular capillary hydraulic pressure and hence the net driving force for ultrafiltration are lower than previously believed. By the efferent end of the glomerular capillary network, net filtration of fluid ceases, owing to a reduction in the net driving force to zero. Evidence in the rat indicates that the process of ultrafiltration is highly dependent on glomerular plasma flow rate. Studies in rats with surface glomeruli have also made possible an assessment of the factors that govern the transport of macromolecules across the highly specialized capillary network. In addition to molecular size, transcapillary movement of macromolecules is influenced by the glomerular filtration rate, since total transport reflects the combined contributions of convection as well as diffusion. Molecular charge has also been found to be an important determinant of the transport of macromolecules, very likely contributing to the marked restriction to the transcapillary movement of albumin. This electrostatic restriction to the transport of polyanions such as albumin, by some fixed, negatively charged component(s) of the glomerular capillary wall, is markedly reduced in primary glomerular injury. Evidence indicates that glomerular injury results in loss of these fixed negative charges from the capillary walls, providing an attractive explanation for the enhanced filtration of albumin, and hence the proteinuria, observed in a variety of glomerulopathic states.
Spatial patterning of response to odors in the peripheral olfactory system
Authors: Moulton D. G.
Published: December 2017

The low odor specificities of the olfactory receptors suggest that odor recognition depends on the simultaneous activity in an ensemble of receptor neurons. This ensemble could conceivably code quality without reference to the point of origin of each input on the receptor sheet. However, the nose-to-bulb projection appears sufficiently precise to provide the bulb with a topographical map of the receptor sheet although it is poorly delineated in the anteroposterior plane. (It is also known that the morphological changes that follow prolonged exposure to odors are more differentiated in the coronal than in the anteroposterior plane.) Furthermore, it is clear from work at both epithelial and bulbar levels that a spatiotemporal pattern of excitation is generated by odor stimulation of the receptor sheet and that this pattern differs for different odors. This evidence, then, supports the view that there is a spatial component to odor quality coding. This spatial pattern has two elements. One is imposed and depends (at least in part) on differences in the retentivity of different odorants by the mucous sheet, which has powerful sorptive properties. It effectiveness seems particularly weak for odorants with relatively long retention times. The second component is inherent and depends on the tendency of receptors with similar peak odor specificities to aggregate in the same region (or regions) of the epithelium. Different odors or groups of odors maximally excite different regions, which may overlap. The imposed component could not, in itself, provide an adequate mechanism for odor recognition, partly because many compounds have comparable or even identical mean retention times (e.g., enantiomeric isomers). The inherent component, on the other hand, possesses this potential. However, either or both forms of patterning may cooperate with a third nonspatial mechanism (based on differential responsiveness of receptors to different odors) in coding odor quality.
Stress-induced analgesia: adaptive pain suppression
Authors: Amit Z. , Galina Z. H.
Published: December 2017

In this paper we have examined the phenomenon of stress-induced analgesia. We have described the procedures used to measure analgesia and have suggested that the tests can be designed not only to indicate changes in pain threshold but also to allow for the determination of the capacity to execute adaptive behavior. Aside from enabling the analysis of responses, tests that induce reflexive as well as nonreflexive behavior may have the capacity to separate the more complex aspects of pain such as the possible presence of two components of pain, sensory/discriminative and motivational/affective. These components may be of fundamental importance for any attempt to understand the biological significance of SIA. Our examination of the neurotransmitter and neuropeptide systems has revealed that they are affected by the same manipulations that induce SIA. These amines and perhaps peptides play an integral role in learning, motivation, and performance. We conclude that the functional advantage of a reduction of pain during stressful situations is significant because it allows the animal to react in threatening and perhaps critical situations as if there were no pain. Once the pain system is inhibited, other systems modulate and mediate adaptive responses that expedite the survival of the animal.
Renal magnesium handling and its hormonal control
Authors: de Rouffignac C. , Quamme G.
Published: December 2017

Our understanding of renal Mg handling has been expanded in recent years with the use of electron probe, ultramicroanalysis, and fluorescent dye techniques to determine total Mg and free Mg2+ in individual tubule segments and cells, respectively. Recent studies have shown that [Mg2+]i is a highly mobile cation that may be altered by a number of influences including hormones. It is likely that the hormonal changes in [Mg2+]i, reported here and elsewhere, are involved in intracellular metabolism and regulation rather than transepithelial transport. The role of intracellular Mg2+ in control of cell function is poorly understood. However, it is evident that [Mg2+]i may be rapidly charged through a number of different influences that may have important effects on cell function. These kinds of data have enlarged our understanding of Mg conservation by the renal tubule but have posed many questions for further study. Magnesium is handled in different ways along the nephron. About 80% of the total plasma Mg (1.5-2.0 mM) is ultrafilterable across the glomerular membrane. Of the ultrafilterable Mg (1.2-1.6 mM), only 20-25% is reabsorbed by the proximal tubule, including the convoluted and straight portions. This is in contrast to Na and Ca reabsorption, which amounts to approximately 70 and 60%, respectively, in the proximal nephron. Accordingly, the fractional delivery of Mg to the thick ascending limb of the loop of Henle is much greater than that of Na or Ca. It is now evident from micropuncture studies that proportionally greater amounts of Mg (50-60%) are reabsorbed in the loop compared with Na (20-25%) or Ca (30-35%). Because the terminal nephron segments, including the DCT and collecting tubule, reabsorb only a small portion of the filtered Mg (approximately 5%), the loop of Henle plays a major role in the determination of Mg reabsorption, and it is in this segment that the major regulatory factors act to maintain Mg balance. Magnesium reabsorption in the thick ascending limb takes place in the cortical segments, at least in the mouse and rat. Evidence summarized here suggests that Mg is passively reabsorbed via the paracellular pathway in the cTAL of the loop of Henle. Several factors affect Mg reabsorption in the loop of Henle. Hypermagnesemia and hypercalcemia inhibit reabsorption leading to increased urinary excretion of Mg and Ca. These effects have been reviewed in detail elsewhere (113, 149). Magnesium depletion, for instance through dietary Mg deprivation, enhances Mg reabsorption in the loop of Henle before the fall in plasma Mg concentration and filtered Mg load.(ABSTRACT TRUNCATED AT 400 WORDS)
Modulation of epithelial permeability by extracellular macromolecules
Authors: Lewis S. A. , Berg J. R. , Kleine T. J.
Published: December 2017

Epithelia are sheets of cells joined together by tight junctions. This geometry allows an epithelium to act as a barrier, i.e., restrict the movement of substances between two compartments that it separates (typically 1 compartment is the blood) and also to actively and selectively transport substances between the two compartments. It has been known for a number of years that both the barrier and transport functions of epithelia can be regulated by hormones and neurotransmitters, and this regulation is a central component of plasma electrolyte and nonelectrolyte homeostasis. Less appreciated is that these epithelial functions can be modified by macromolecules other than neurotransmitters and hormones. These macromolecules have been divided into the following categories: proteases, cytokines, cellular constituents, nonbacterial xenobiotics, and bacterial xenobiotics. Such macromolecules can alter epithelial transport and barrier function by a number of different mechanisms. These include proteolysis of epithelial ion channels and tight junctional complexes, conversion of an ion pump into a nonselective cation channel, increase in epithelial membrane permeability resulting in cell swelling and lysis, and up- or downregulation of cellular second messenger systems that can alter ion transport capabilities or prove cytotoxic to the cells. Finally, these modifications can be either transient or chronic in nature and in many circumstances result in a perturbation of the electrolyte and nonelectrolyte status of the host organism.
Properties and regulation of the minK potassium channel protein
Authors: Kaczmarek L. K. , Blumenthal E. M.
Published: December 2017

The minK gene encodes a protein of 130 amino acids that has a single transmembrane segment and is expressed in many tissues including heart, uterus, and kidney. When Xenopus oocytes are injected with minK mRNA, a very slowly activating voltage-dependent potassium current is induced in these cells. The induced channels appear to result from the interaction of the minK protein with other channel-forming subunits such as the KvLQT1 channel. The minK protein is intimately associated with the structure of the resultant channels, and mutations in minK can alter ion selectivity and modulation by second messengers. Strong candidates for native currents regulated by the minK protein include the slow component of the cardiac delayed rectifier and potassium currents recorded across epithelial cells in vestibular organs and cochlea.
Cold-Induced Thermoregulation and Biological Aging
Authors: FLOREZ-DUQUET MARIA , McDONALD ROGER B.
Published: December 2017

Florez-Duquet, Maria, and Roger B. McDonald. Cold-Induced Thermoregulation and Biological Aging. Physiol. Rev. 78: 339–358, 1998. — Aging is associated with diminished cold-induced thermoregulation (CIT). The mechanisms accounting for this phenomenon have yet to be clearly elucidated but most likely reflect a combination of increased heat loss and decreased metabolic heat production. The inability of the aged subject to reduce heat loss during cold exposure is associated with diminished reactive tone of the cutaneous vasculature and, to a lesser degree, alterations in the insulative properties of body fat. Cold-induced metabolic heat production via skeletal muscle shivering thermogenesis and brown adipose tissue nonshivering thermogenesis appears to decline with age. Few investigations have directly linked diminished skeletal muscle shivering thermogenesis with the age-related reduction in cold-induced thermoregulatory capacity. Rather, age-related declines in skeletal muscle mass and metabolic activity are cited as evidence for decreased heat production via shivering. Reduced mass, GDP binding to brown fat mitochondria, and uncoupling protein (UCP) levels are cited as evidence for attenuated brown adipose tissue cold-induced nonshivering thermogenic capacity during aging. The age-related reduction in brown fat nonshivering thermogenic capacity most likely reflects altered cellular signal transduction rather than changes in neural and hormonal signaling. The discussion in this review focuses on how alterations in CIT during the life span may offer insight into possible mechanisms of biological aging. Although the preponderance of evidence presented here demonstrates that CIT declines with chronological time, the mechanism reflecting this attenuated function remains to be elucidated. The inability to draw definitive conclusions regarding biological aging and CIT reflects the lack of a clear definition of aging. It is unlikely that the mechanisms accounting for the decline in cold-induced thermoregulation during aging will be determined until biological aging is more precisely defined.
Effects of Serine/Threonine Protein Phosphatases on Ion Channels in Excitable Membranes
Authors: Herzig Stefan , Neumann Joachim
Published: December 2017

This review deals with the influence of serine/threonine-specific protein phosphatases on the function of ion channels in the plasma membrane of excitable tissues. Particular focus is given to developments of the past decade. Most of the electrophysiological experiments have been performed with protein phosphatase inhibitors. Therefore, a synopsis is required incorporating issues from biochemistry, pharmacology, and electrophysiology. First, we summarize the structural and biochemical properties of protein phosphatase (types 1, 2A, 2B, 2C, and 3–7) catalytic subunits and their regulatory subunits. Then the available pharmacological tools (protein inhibitors, nonprotein inhibitors, and activators) are introduced. The use of these inhibitors is discussed based on their biochemical selectivity and a number of methodological caveats. The next section reviews the effects of these tools on various classes of ion channels (i.e., voltage-gated Ca2+and Na+channels, various K+channels, ligand-gated channels, and anion channels). We delineate in which cases a direct interaction between a protein phosphatase and a given channel has been proven and where a more complex regulation is likely involved. Finally, we present ideas for future research and possible pathophysiological implications.
Role of Alternative Splicing in Generating Isoform Diversity Among Plasma Membrane Calcium Pumps
Authors: Strehler Emanuel E. , Zacharias David A.
Published: December 2017

Calcium pumps of the plasma membrane (also known as plasma membrane Ca2+-ATPases or PMCAs) are responsible for the expulsion of Ca2+from the cytosol of all eukaryotic cells. Together with Na+/Ca2+exchangers, they are the major plasma membrane transport system responsible for the long-term regulation of the resting intracellular Ca2+concentration. Like the Ca2+pumps of the sarco/endoplasmic reticulum (SERCAs), which pump Ca2+from the cytosol into the endoplasmic reticulum, the PMCAs belong to the family of P-type primary ion transport ATPases characterized by the formation of an aspartyl phosphate intermediate during the reaction cycle. Mammalian PMCAs are encoded by four separate genes, and additional isoform variants are generated via alternative RNA splicing of the primary gene transcripts. The expression of different PMCA isoforms and splice variants is regulated in a developmental, tissue- and cell type-specific manner, suggesting that these pumps are functionally adapted to the physiological needs of particular cells and tissues. PMCAs 1 and 4 are found in virtually all tissues in the adult, whereas PMCAs 2 and 3 are primarily expressed in excitable cells of the nervous system and muscles. During mouse embryonic development, PMCA1 is ubiquitously detected from the earliest time points, and all isoforms show spatially overlapping but distinct expression patterns with dynamic temporal changes occurring during late fetal development. Alternative splicing affects two major locations in the plasma membrane Ca2+pump protein: the first intracellular loop and the COOH-terminal tail. These two regions correspond to major regulatory domains of the pumps. In the first cytosolic loop, the affected region is embedded between a putative G protein binding sequence and the site of phospholipid sensitivity, and in the COOH-terminal tail, splicing affects pump regulation by calmodulin, phosphorylation, and differential interaction with PDZ domain-containing anchoring and signaling proteins. Recent evidence demonstrating differential distribution, dynamic regulation of expression, and major functional differences between alternative splice variants suggests that these transporters play a more dynamic role than hitherto assumed in the spatial and temporal control of Ca2+signaling. The identification of mice carrying PMCA mutations that lead to diseases such as hearing loss and ataxia, as well as the corresponding phenotypes of genetically engineered PMCA “knockout” mice further support the concept of specific, nonredundant roles for each Ca2+pump isoform in cellular Ca2+regulation.
Multimodality Treatment Including Triplet Regimen as First-Line Chemotherapy May Improve Prognosis of Serum AFP-Elevated Gastric Cancer with Liver Metastasis
Authors: Wang Yakun , Shen Lin , Lu Ming , Ji Zhi , Zhang Xiaotian
Published: December 2017

Serum α-fetoprotein- (AFP-) elevated gastric cancer is a rare tumor that has a poor prognosis due to high incidence of liver metastasis. This study sought to investigate the optimal treatment modality. A total of 319 gastric cancer patients with liver metastasis (GCLM) whose serum AFP levels were tested before treatment were enrolled in this study. They were classified as the serum AFP ≥ 20 ng/ml group (n=74) and the AFP < 20 ng/ml group (n=245). Median OS of the AFP < 20 ng/ml group was significantly longer than that of the AFP ≥ 20 ng/ml group (15.7 m versus 10.9 m, P=0.004). ORR of first-line chemotherapy was 43.3% and 56.1% of the two groups, respectively (P=0.024). Of patients who received doublet regimen, ORR of the AFP ≥ 20 ng/ml group was significantly lower (38.2 versus 56.9%, P=0.013), while in those received triplet regimens, ORR between two groups was similar (66.7% versus 66.7%, P=0.676). Moreover, for patients of the AFP ≥ 20 ng/ml group, those who reached PR had a longer survival period (15.4 m versus 9.4 m, P=0.017), and combined with local treatment for liver metastasis also seemed to improve prognosis (19.2 m versus 8.4 m, P=0.003). In conclusion, serum AFP-elevated GCLM had a poorer prognosis. Multimodality treatment including aggressive first-line chemotherapy with triplet regimen may be needed when treating them.
Energy-Momentum for a Charged Nonsingular Black Hole Solution with a Nonlinear Mass Function
Authors: Radinschi Irina , Grammenos Theophanes , Rahaman Farook , Spanou Andromahi , Islam Sayeedul , Chattopadhyay Surajit , Pasqua Antonio
Published: December 2017

The energy-momentum of a new four-dimensional, charged, spherically symmetric, and nonsingular black hole solution constructed in the context of general relativity coupled to a theory of nonlinear electrodynamics is investigated, whereby the nonlinear mass function is inspired by the probability density function of the continuous logistic distribution. The energy and momentum distributions are calculated by use of the Einstein, Landau-Lifshitz, Weinberg, and Møller energy-momentum complexes. In all these prescriptions, it is found that the energy distribution depends on the mass M and the charge q of the black hole, an additional parameter β coming from the gravitational background considered, and the radial coordinate r. Further, the Landau-Lifshitz and Weinberg prescriptions yield the same result for the energy, while, in all the aforesaid prescriptions, all the momenta vanish. We also focus on the study of the limiting behavior of the energy for different values of the radial coordinate, the parameter β, and the charge q. Finally, it is pointed out that, for r→∞ and q=0, all the energy-momentum complexes yield the same expression for the energy distribution as in the case of the Schwarzschild black hole solution.