scholarly journals Distinct co-modulation rules of synaptic and voltage-gated currents coordinates interactions of multiple neuromodulators

2018 ◽  
Author(s):  
Xinping Li ◽  
Dirk Bucher ◽  
Farzan Nadim
Keyword(s):  
Signaling Pathways ◽  
Ionic Currents ◽  
Evolutionary Conservation ◽  
Stomatogastric Ganglion ◽  
Cancer Borealis ◽  
Voltage Gated ◽  
Individual Effects ◽  
The Individual ◽  
Circuit Output ◽  
Dose Dependent

AbstractDifferent neuromodulators usually activate distinct receptors but can have overlapping targets. Consequently, circuit output depends on neuromodulator interactions at shared targets, a poorly understood process. We explored quantitative rules of co-modulation of two principal targets: voltage-gated and synaptic ionic currents. In the stomatogastric ganglion of the crab Cancer borealis, the neuropeptides proctolin and CCAP modulate synapses of the pyloric circuit, and activate a voltage-gated current (IMI) in multiple neurons. We examined the validity of a simple dose-dependent quantitative rule that co-modulation by proctolin and CCAP is predicted by the linear sum of the individual effects of each modulator, up to saturation. We found that this rule is valid for co-modulation of synapses, but not for the activation of IMI, where co-modulation was sublinear. Given the evolutionary conservation of neuromodulator receptors and signaling pathways, such distinct rules for co-modulation of different targets are likely to be common across neuronal circuits.

The effects of SDRNFLRFamide and TNRNFLRFamide on the motor patterns of the stomatogastric ganglion of the crab Cancer borealis

1993 ◽  
Vol 181 (1) ◽  
pp. 1-26 ◽  
Author(s):  
J. M. Weimann ◽  
E. Marder ◽  
B. Evans ◽  
R. L. Calabrese
Keyword(s):  
Nervous System ◽  
High Performance ◽  
Stomatogastric Ganglion ◽  
Moderate Activity ◽  
Activity Levels ◽  
Dependent Manner ◽  
Stomatogastric Nervous System ◽  
Cancer Borealis ◽  
Motor Patterns ◽  
Dose Dependent

TNRNFLRFamide was isolated and sequenced from the stomatogastric nervous system of the crab Cancer borealis by reverse-phase high performance liquid chromatography followed by automated Edman degradation. An SDRNFLRFamide-like peptide that exactly co-migrated with SDRNFLRFamide was also observed. The effects of TNRNFLRFamide and SDRNFLRFamide on the gastric and pyloric rhythms of the stomatogastric nervous system of the crab Cancer borealis were studied. Both peptides activated pyloric rhythms in quiescent preparations in a dose-dependent manner with a threshold between 10(−11) and 10(−10) mol l-1. Both peptides increased the pyloric rhythm frequency of preparations showing moderate activity levels and had relatively little effect on preparations that showed strong pyloric rhythms prior to peptide application. Both peptides evoked gastric mill activity in preparations without existing gastric rhythms. The activation of the gastric rhythm is associated with activation of oscillatory properties in the dorsal gastric neurone. The induction of gastric rhythms by these peptides was accompanied by switches from pyloric-timed activity to gastric-timed activity by several stomatogastric ganglion neurones. Application of these peptides provides direct experimental control of circuit modification in the stomatogastric nervous system.

Mathematical model of an identified stomatogastric ganglion neuron

1992 ◽  
Vol 67 (2) ◽  
pp. 332-340 ◽  
Author(s):  
F. Buchholtz ◽  
J. Golowasch ◽  
I. R. Epstein ◽  
E. Marder
Keyword(s):  
Preceding Paper ◽  
Outward Current ◽  
Ionic Currents ◽  
Stomatogastric Ganglion ◽  
Delayed Rectifier ◽  
Cancer Borealis ◽  
Similar Action ◽  
Steady State Current ◽  
Voltage Dependent ◽  
Rock Crab

1. The ionic currents in the lateral pyloric (LP) cell of the stomatogastric ganglion (STG) described in the preceding paper of the rock crab Cancer borealis were fit with a set of differential equations that describe their voltage, time, and Ca2+ dependence. The voltage-dependent currents modeled are a delayed rectifier-like current, id; a Ca(2+)-activated outward current, io(Ca); a transient A-like current, iA; a Ca2+ current, iCa; an inwardly rectifying current, ih; and a fast tetrodotoxin (TTX)-sensitive Na+ current, iNa. 2. A single-compartment, isopotential model of the LP cell was constructed from the six voltage-dependent currents, a voltage-independent leak current il, a Ca2+ buffering system, and the membrane capacitance. 3. The behavior of the model LP neuron was compared with that of the biological neuron by simulating physiological experiments carried out in both voltage-clamp and current-clamp modes. The model and biological neurons show similar action-potential shapes, durations, steady-state current-voltage (I-V) curves, and respond to injected current in a comparable way.

scholarly journals Characterization of Direct Perturbations on Voltage-Gated Sodium Current by Esaxerenone, a Nonsteroidal Mineralocorticoid Receptor Blocker

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 549
Author(s):  
Wei-Ting Chang ◽  
Sheng-Nan Wu
Keyword(s):  
Mineralocorticoid Receptor ◽  
Sodium Current ◽  
Ionic Currents ◽  
Antagonistic Effect ◽  
Gh3 Cells ◽  
Excitable Cells ◽  
Voltage Gated ◽  
Ic50 Value ◽  
Low Threshold

Esaxerenone (ESAX; CS-3150, Minnebro®) is known to be a newly non-steroidal mineralocorticoid receptor (MR) antagonist. However, its modulatory actions on different types of ionic currents in electrically excitable cells remain largely unanswered. The present investigations were undertaken to explore the possible perturbations of ESAX on the transient, late and persistent components of voltage-gated Na+ current (INa) identified from pituitary GH3 or MMQ cells. GH3-cell exposure to ESAX depressed the transient and late components of INa with varying potencies. The IC50 value of ESAX required for its differential reduction in peak or late INa in GH3 cells was estimated to be 13.2 or 3.2 μM, respectively. The steady-state activation curve of peak INa remained unchanged during exposure to ESAX; however, recovery of peak INa block was prolonged in the presence 3 μM ESAX. In continued presence of aldosterone (10 μM), further addition of 3 μM ESAX remained effective at inhibiting INa. ESAX (3 μM) potently reversed Tef-induced augmentation of INa. By using isosceles-triangular ramp pulse with varying durations, the amplitude of persistent INa measured at high or low threshold was enhanced by the presence of tefluthrin (Tef), in combination with the appearance of the figure-of-eight hysteretic loop; moreover, hysteretic strength of the current was attenuated by subsequent addition of ESAX. Likewise, in MMQ lactotrophs, the addition of ESAX also effectively decreased the peak amplitude of INa along with the increased current inactivation rate. Taken together, the present results provide a noticeable yet unidentified finding disclosing that, apart from its antagonistic effect on MR receptor, ESAX may directly and concertedly modify the amplitude, gating properties and hysteresis of INa in electrically excitable cells.

scholarly journals Biological Effect of Different Spinach Extracts in Comparison with the Individual Components of the Phytocomplex

Foods ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 382
Author(s):  
Laura Arru ◽  
Francesca Mussi ◽  
Luca Forti ◽  
Annamaria Buschini
Keyword(s):  
Antioxidant Defense ◽  
Extraction Methods ◽  
Oxidizing Agent ◽  
Endogenous Reactive Oxygen Species ◽  
Dependent Activity ◽  
Main Components ◽  
The Individual ◽  
Dose Dependent ◽  
Higher Doses ◽  
Oxidative Insult

The Mediterranean-style diet is rich in fruit and vegetables and has a great impact on the prevention of major chronic diseases, such as cardiovascular diseases and cancer. In this work we investigated the ability of spinach extracts obtained by different extraction methods and of the single main components of the phytocomplex, alone or mixed, to modulate proliferation, antioxidant defense, and genotoxicity of HT29 human colorectal cells. Spinach extracts show dose-dependent activity, increasing the level of intracellular endogenous reactive oxygen species (ROS) when tested at higher doses. In the presence of oxidative stress, the activity is related to the oxidizing agent involved (H2O2 or menadione) and by the extraction method. The single components of the phytocomplex, alone or mixed, do not alter the intracellular endogenous level of ROS but again, in the presence of an oxidative insult, the modulation of antioxidant defense depends on the oxidizing agent used. The application of the phytocomplex extracts seem to be more effective than the application of the single phytocomplex components.

ALTERNATIVE ROUTES TO INNOVATION — THE EFFECTS OF CULTURAL AND STRUCTURAL FIT

2019 ◽  
Vol 24 (01) ◽  
pp. 2050006
Author(s):  
DAG INGVAR JACOBSEN ◽  
TORE HILLESTAD ◽  
BIRGITTE YTTRI ◽  
JARLE HILDRUM
Keyword(s):  
Response Rate ◽  
Organic Structure ◽  
Configurational Approach ◽  
Culture Strength ◽  
Individual Effects ◽  
Collective Phenomenon ◽  
The Individual ◽  
Alternative Routes ◽  
Innovative Culture ◽  
The Empirical Analysis

A configurational approach to organizations assumes that structural and cultural characteristics must be in “fit” to produce the wanted outcome. With a focus on innovation, this study examines empirically to what extent innovative activities with a large, global telecom company are produced by an innovative culture, an innovative structure, as well as the fit between the two. Based on an extensive survey (N = 21064, response rate = 65) of employees in seven countries in Europe and Asia, data was aggregated to unit level as culture by nature is a collective phenomenon. The empirical analysis detected both the individual effects of culture strength and homogeneity, structure, as well as the fit between the two. The results indicate that an innovative culture and an organic structure indeed fosters innovation, but that, somewhat surprisingly, there are not effects of the fit between the two. Both practical and theoretical implications are discussed.

Factors influencing the individual effects of blood transfusions on oxygen delivery and oxygen consumption*

2001 ◽  
Vol 29 (Supplement) ◽  
pp. S173-S179 ◽  
Author(s):  
Mattias Casutt ◽  
Burkhardt Seifert ◽  
Thomas Pasch ◽  
Edith R. Schmid ◽  
Marko I. Turina ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Oxygen Delivery ◽  
Blood Transfusions ◽  
Factors Influencing ◽  
Individual Effects ◽  
The Individual

scholarly journals Ancient Origins and Evolutionary Conservation of Intracellular and Neural Signaling Pathways Engaged by the Leptin Receptor

Endocrinology ◽  
2014 ◽  
Vol 155 (11) ◽  
pp. 4202-4214 ◽  
Author(s):  
Melissa Y. Cui ◽  
Caroline K. Hu ◽  
Chris Pelletier ◽  
Adam Dziuba ◽  
Rose H. Slupski ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Leptin Receptor ◽  
Evolutionary Conservation ◽  
Neural Signaling

scholarly journals Influence of process variables on release properties of paracetamol tablets

2007 ◽  
Vol 57 (1) ◽  
pp. 73-86 ◽  
Author(s):  
Gbenga Alebiowu ◽  
Oludele Itiola
Keyword(s):  
Interaction Effects ◽  
Process Variables ◽  
Factorial Experimental Design ◽  
Disintegration Time ◽  
Individual Effects ◽  
Pregelatinized Starch ◽  
Tablet Formulations ◽  
Binder Concentration ◽  
The Individual ◽  
Paracetamol Tablet

Influence of process variables on release properties of paracetamol tablets A 23 factorial experimental design has been used to quantitatively study individual and interaction effects of the nature of binder (N), binder concentration (c) and relative density of tablet (d) on the disintegration time (DT) and dissolution times, t1, t50 and t90, of paracetamol tablet formulations. The factorial design was also used to study the quantitative effects of pregelatinization of starch binders on these parameters, i.e., N, c and d. In general, the most common ranking of the individual effects on DT, t1, t50 and t90 for native/native, pregelatinized/pregelatinized and native/pregelatinized starch binder formulations was c > d > N. For interaction effects, the most common ranking was N-c > c-d > N-d for all formulations. The results generally showed that c can considerably affect DT, t1, t50 and t90 of the tablets.

Dopamine Modulation of Calcium Currents in Pyloric Neurons of the Lobster Stomatogastric Ganglion

2003 ◽  
Vol 90 (2) ◽  
pp. 631-643 ◽  
Author(s):  
Bruce R. Johnson ◽  
Peter Kloppenburg ◽  
Ronald M. Harris-Warrick
Keyword(s):  
Calcium Channel ◽  
Transmitter Release ◽  
Stomatogastric Ganglion ◽  
Calcium Currents ◽  
Voltage Gated ◽  
Pyloric Network ◽  
Pyloric Dilator ◽  
Voltage Dependent ◽  
Inward Currents ◽  
Dopamine Modulation

We examined the dopamine (DA) modulation of calcium currents (ICa) that could contribute to the plasticity of the pyloric network in the lobster stomatogastric ganglion. Pyloric somata were voltage-clamped under conditions designed to block voltage-gated Na+, K+, and H currents. Depolarizing steps from –60 mV generated voltage-dependent, inward currents that appeared to originate in electrotonically distal, imperfectly clamped regions of the cell. These currents were blocked by Cd2+ and enhanced by Ba2+ but unaffected by Ni2+. Dopamine enhanced the peak ICa in the pyloric constrictor (PY), lateral pyloric (LP), and inferior cardiac (IC) neurons and reduced peak ICa in the ventricular dilator (VD), pyloric dilator (PD), and anterior burster (AB) neurons. All of these effects, except for the AB, are consistent with DA's excitation or inhibition of firing in the pyloric neurons. Enhancement of ICa in PY and LP neurons and reduction of ICa in VD and PD neurons are also consistent with DA-induced synaptic strength changes via modulation of presynaptic ICa. However, the reduction of ICa in AB suggests that DA's enhancement of AB transmitter release is not directly mediated through presynaptic ICa. ICa in PY and PD neurons was more sensitive to nifedipine block than in AB neurons. In addition, nifedipine blocked DA's effects on ICa in the PY and PD neurons but not in the AB neuron. Thus the contribution of specific calcium channel subtypes carrying the total ICa may vary between pyloric neuron classes, and DA may act on different calcium channel subtypes in the different pyloric neurons.

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