scholarly journals Ionic mechanisms and Ca2+ dynamics underlying the glucose response of pancreatic β cells: a simulation study

2011 ◽  
Vol 138 (1) ◽  
pp. 21-37 ◽  
Author(s):  
Chae Young Cha ◽  
Yasuhiko Nakamura ◽  
Yukiko Himeno ◽  
JianWu Wang ◽  
Shinpei Fujimoto ◽  
...  
Keyword(s):  
Action Potentials ◽  
Cell Model ◽  
Repetitive Firing ◽  
Glucose Response ◽  
Slow Potential ◽  
Ionic Mechanisms ◽  
K Current ◽  
Experimental Findings ◽  
Functional Components

To clarify the mechanisms underlying the pancreatic β-cell response to varying glucose concentrations ([G]), electrophysiological findings were integrated into a mathematical cell model. The Ca2+ dynamics of the endoplasmic reticulum (ER) were also improved. The model was validated by demonstrating quiescent potential, burst–interburst electrical events accompanied by Ca2+ transients, and continuous firing of action potentials over [G] ranges of 0–6, 7–18, and >19 mM, respectively. These responses to glucose were completely reversible. The action potential, input impedance, and Ca2+ transients were in good agreement with experimental measurements. The ionic mechanisms underlying the burst–interburst rhythm were investigated by lead potential analysis, which quantified the contributions of individual current components. This analysis demonstrated that slow potential changes during the interburst period were attributable to modifications of ion channels or transporters by intracellular ions and/or metabolites to different degrees depending on [G]. The predominant role of adenosine triphosphate–sensitive K+ current in switching on and off the repetitive firing of action potentials at 8 mM [G] was taken over at a higher [G] by Ca2+- or Na+-dependent currents, which were generated by the plasma membrane Ca2+ pump, Na+/K+ pump, Na+/Ca2+ exchanger, and TRPM channel. Accumulation and release of Ca2+ by the ER also had a strong influence on the slow electrical rhythm. We conclude that the present mathematical model is useful for quantifying the role of individual functional components in the whole cell responses based on experimental findings.

scholarly journals The modulation of two motor behaviors by persistent sodium currents in Xenopus laevis tadpoles

2017 ◽  
Vol 118 (1) ◽  
pp. 121-130 ◽  
Author(s):  
Erik Svensson ◽  
Hugo Jeffreys ◽  
Wen-Chang Li
Keyword(s):  
Action Potentials ◽  
Sodium Current ◽  
Repetitive Firing ◽  
Sodium Currents ◽  
Spinal Neurons ◽  
Motor Behaviors ◽  
Low Concentrations ◽  
Descending Interneurons ◽  
Lateral Sclerosis

Persistent sodium currents ( INaP) are common in neuronal circuitries and have been implicated in several diseases, such as amyotrophic lateral sclerosis (ALS) and epilepsy. However, the role of INaP in the regulation of specific behaviors is still poorly understood. In this study we have characterized INaP and investigated its role in the swimming and struggling behavior of Xenopus tadpoles. INaP was identified in three groups of neurons, namely, sensory Rohon-Beard neurons (RB neurons), descending interneurons (dINs), and non-dINs (neurons rhythmically active in swimming). All groups of neurons expressed INaP, but the currents differed in decay time constants, amplitudes, and the membrane potential at which INaP peaked. Low concentrations (1 µM) of the INaP blocker riluzole blocked INaP ~30% and decreased the excitability of the three neuron groups without affecting spike amplitudes or cellular input resistances. Riluzole reduced the number of rebound spikes in dINs and depressed repetitive firing in RB neurons and non-dINs. At the behavior level, riluzole at 1 µM shortened fictive swimming episodes. It also reduced the number of action potentials neurons fired on each struggling cycle. The results show that INaP may play important modulatory roles in motor behaviors. NEW & NOTEWORTHY We have characterized persistent sodium currents in three groups of spinal neurons and their role in shaping spiking activity in the Xenopus tadpole. We then attempted to evaluate the role of persistent sodium currents in regulating tadpole swimming and struggling motor outputs by using low concentrations of the persistent sodium current antagonist riluzole.

scholarly journals Calcium-activated K+ Channels of Mouse β-cells are Controlled by Both Store and Cytoplasmic Ca2+

2002 ◽  
Vol 120 (3) ◽  
pp. 307-322 ◽  
Author(s):  
P.B. Goforth ◽  
R. Bertram ◽  
F.A. Khan ◽  
M. Zhang ◽  
A. Sherman ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Action Potentials ◽  
Potassium Current ◽  
Cytosolic Calcium ◽  
Β Cells ◽  
Calcium Dependent ◽  
Extracellular Glucose Concentration ◽  
Extracellular Glucose ◽  
Experimental Findings

A novel calcium-dependent potassium current (Kslow) that slowly activates in response to a simulated islet burst was identified recently in mouse pancreatic β-cells (Göpel, S.O., T. Kanno, S. Barg, L. Eliasson, J. Galvanovskis, E. Renström, and P. Rorsman. 1999. J. Gen. Physiol. 114:759–769). Kslow activation may help terminate the cyclic bursts of Ca2+-dependent action potentials that drive Ca2+ influx and insulin secretion in β-cells. Here, we report that when [Ca2+]i handling was disrupted by blocking Ca2+ uptake into the ER with two separate agents reported to block the sarco/endoplasmic calcium ATPase (SERCA), thapsigargin (1–5 μM) or insulin (200 nM), Kslow was transiently potentiated and then inhibited. Kslow amplitude could also be inhibited by increasing extracellular glucose concentration from 5 to 10 mM. The biphasic modulation of Kslow by SERCA blockers could not be explained by a minimal mathematical model in which [Ca2+]i is divided between two compartments, the cytosol and the ER, and Kslow activation mirrors changes in cytosolic calcium induced by the burst protocol. However, the experimental findings were reproduced by a model in which Kslow activation is mediated by a localized pool of [Ca2+] in a subspace located between the ER and the plasma membrane. In this model, the subspace [Ca2+] follows changes in cytosolic [Ca2+] but with a gradient that reflects Ca2+ efflux from the ER. Slow modulation of this gradient as the ER empties and fills may enhance the role of Kslow and [Ca2+] handling in influencing β-cell electrical activity and insulin secretion.

Role of Voltage-Gated K+ Currents in Mediating the Regular-Spiking Phenotype of Callosal-Projecting Rat Visual Cortical Neurons

1997 ◽  
Vol 78 (5) ◽  
pp. 2321-2335 ◽  
Author(s):  
Rachel E. Locke ◽  
Jeanne M. Nerbonne
Keyword(s):  
Action Potential ◽  
Cortical Neurons ◽  
Action Potentials ◽  
Repetitive Firing ◽  
Functional Roles ◽  
Firing Rates ◽  
Voltage Gated ◽  
Firing Properties ◽  
Visual Cortical

Locke, Rachel E. and Jeanne M. Nerbonne. Role of voltage-gated K+ currents in mediating the regular-spiking phenotype of callosal-projecting rat visual cortical neurons. J. Neurophysiol. 78: 2321–2335, 1997. Whole cell current- and voltage-clamp recordings were combined to examine action potential waveforms, repetitive firing patterns, and the functional roles of voltage-gated K+ currents ( I A, I D, and I K) in identified callosal-projecting (CP) neurons from postnatal (day 7–13) rat primary visual cortex. Brief (1 ms) depolarizing current injections evoke single action potentials in CP neurons with mean ± SD ( n = 60) durations at 50 and 90% repolarization of 1.9 ± 0.5 and 5.5 ± 2.0 ms, respectively; action potential durations in individual cells are correlated inversely with peak outward current density. During prolonged threshold depolarizing current injections, CP neurons fire repetitively, and two distinct, noninterconverting “regular-spiking” firing patterns are evident: weakly adapting CP cells fire continuously, whereas strongly adapting CP cells cease firing during maintained depolarizing current injections. Action potential repolarization is faster and afterhyperpolarizations are more pronounced in strongly than in weakly adapting CP cells. In addition, input resistances are lower and plateau K+ current densities are higher in strongly than in weakly adapting CP cells. Functional studies reveal that blockade of I D reduces the latency to firing an action potential, and increases action potential durations at 50 and 90% repolarization. Blockade of I D also increases firing rates in weakly adapting cells and results in continuous firing of strongly adapting cells. After applications of millimolar concentrations of 4-aminopyridine to suppress I A (as well as block I D), action potential durations at 50 and 90% repolarization are further increased, and firing rates are accelerated over those observed when only I D is blocked. Using VClamp/CClamp and the voltage-clamp data in the preceding paper, mathematical descriptions of I A, I D, and I K are generated and a model of the electrophysiological properties of rat visual cortical CP neurons is developed. The model is used to simulate the firing properties of strongly adapting and weakly adapting CP cells and to explore the functional roles of I A, I D, and I K in shaping the waveforms of individual action potentials and controlling the repetitive firing properties of these cells.

scholarly journals Physiological role of dendrotoxin sensitive k channels in the rat cerebellar Purkinje neurons

2007 ◽  
pp. 807-813 ◽  
Author(s):  
H Haghdoust ◽  
M Janahmadi ◽  
G Behzadi
Keyword(s):  
Action Potentials ◽  
Physiological Role ◽  
Neuronal Firing ◽  
Purkinje Neurons ◽  
Repetitive Firing ◽  
Neuronal Membrane ◽  
K Channels ◽  
Type K ◽  
Cerebellar Purkinje Neurons

To understand the contribution of potassium (K+) channels, particularly alpha-dendrotoxin (D-type)-sensitive K+ channels (Kv.1, Kv1.2 or Kv1.6 subunits), to the generation of neuronal spike output we must have detailed information of the functional role of these channels in the neuronal membrane. Conventional intracellular recording methods in current clamp mode were used to identify the role of alpha-dendrotoxin (alpha-DTX)-sensitive K+ channel currents in shaping the spike output and modulation of neuronal properties of cerebellar Purkinje neurons (PCs) in slices. Addition of alpha-DTX revealed that D-type K+ channels play an important role in the shaping of Purkinje neuronal firing behavior. Repetitive firing capability of PCs was increased following exposure to artificial cerebrospinal fluid (aCSF) containing alpha-DTX, so that in response to the injection of 0.6 nA depolarizing current pulse of 600 ms, the number of action potentials insignificantly increased from 15 in the presence of 4-AP to 29 action potentials per second after application of DTX following pretreatment with 4-AP. These results indicate that D-type K+ channels (Kv.1, Kv1.2 or Kv1.6 subunits) may contribute to the spike frequency adaptation in PCs. Our findings suggest that the activation of voltage-dependent K+ channels (D and A types) markedly affect the firing pattern of PCs.

scholarly journals Characterization of swelling behavior of carbon nano-filler modified polydimethylsiloxane composites

2021 ◽  
pp. 009524432110061
Author(s):  
Bo Yang ◽  
Balakrishnan Nagarajan ◽  
Pierre Mertiny
Keyword(s):  
Digital Image Analysis ◽  
Swelling Behavior ◽  
Optical Measurements ◽  
Natural Phenomenon ◽  
Cross Linking ◽  
Dimensional Changes ◽  
Experimental Findings ◽  
Carbon Based

Polymers may absorb fluids from their surroundings via the natural phenomenon of swelling. Dimensional changes due to swelling can affect the function of polymer components, such as in the case of seals, microfluidic components and electromechanical sensors. An understanding of the swelling behavior of polymers and means for controlling it can improve the design of polymer components, for example, for the previously mentioned applications. Carbon-based fillers have risen in popularity to be used for the property enhancement of resulting polymer composites. The present investigation focuses on the effects of three carbon-based nano-fillers (graphene nano-platelets, carbon black, and graphene nano-scrolls) on the dimensional changes of polydimethylsiloxane composites due to swelling when immersed in certain organic solvents. For this study, a facile and expedient methodology comprised of optical measurements in conjunction with digital image analysis was developed as the primary experimental technique to quantify swelling dimensional changes of the prepared composites. Other experimental techniques assessed polymer cross-linking densities and elastic mechanical properties of the various materials. The study revealed that the addition of certain carbon-based nano-fillers increased the overall swelling of the composites. The extent of swelling further depended on the organic solvent in which the composites were immersed in. Experimental findings are contrasted with published models for swelling prediction, and the role of filler morphology on swelling behavior is discussed.

scholarly journals Tetrodotoxin: A New Strategy to Treat Visceral Pain?

Toxins ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 496
Author(s):  
Ana Campos-Ríos ◽  
Lola Rueda-Ruzafa ◽  
Salvador Herrera-Pérez ◽  
Paula Rivas-Ramírez ◽  
José Antonio Lamas
Keyword(s):  
Action Potentials ◽  
Channel Blocker ◽  
Visceral Pain ◽  
Visceral Hypersensitivity ◽  
Afferent Neurons ◽  
Sodium Channel Blocker ◽  
Voltage Gated Sodium Channels ◽  
New Strategy ◽  
Specific Receptors

Visceral pain is one of the most common symptoms associated with functional gastrointestinal (GI) disorders. Although the origin of these symptoms has not been clearly defined, the implication of both the central and peripheral nervous systems in visceral hypersensitivity is well established. The role of several pathways in visceral nociception has been explored, as well as the influence of specific receptors on afferent neurons, such as voltage-gated sodium channels (VGSCs). VGSCs initiate action potentials and dysfunction of these channels has recently been associated with painful GI conditions. Current treatments for visceral pain generally involve opioid based drugs, ≠≠which are associated with important side-effects and a loss of effectiveness or tolerance. Hence, efforts have been intensified to find new, more effective and longer-lasting therapies. The implication of VGSCs in visceral hypersensitivity has drawn attention to tetrodotoxin (TTX), a relatively selective sodium channel blocker, as a possible and promising molecule to treat visceral pain and related diseases. As such, here we will review the latest information regarding this toxin that is relevant to the treatment of visceral pain and the possible advantages that it may offer relative to other treatments, alone or in combination.

Tetrodotoxin-resistant release of ATP from superfused rabbit detrusor muscle during electrical field stimulation in the presence of luciferin–luciferase

1984 ◽  
Vol 62 (1) ◽  
pp. 153-156 ◽  
Author(s):  
Archana Chaudhry ◽  
John W. Downie ◽  
Thomas D. White
Keyword(s):  
Action Potentials ◽  
Electrical Field Stimulation ◽  
Detrusor Muscle ◽  
Electrical Field ◽  
Stimulation Parameters ◽  
Rabbit Bladder ◽  
Firefly Luciferin ◽  
Rabbit Urinary Bladder ◽  
Stimulation Of

The present study was carried out to assess the possible role of ATP in the noncholinergic, nonadrenergic transmission in the rabbit urinary bladder. When rabbit detrusor muscle strips were superfused with medium containing firefly luciferin–luciferase and stimulated transmurally at low stimulation parameters, tetrodotoxin-sensitive contractions were obtained but no release of ATP could be detected. However, at somewhat higher stimulation parameters, release of ATP was observed. This release of ATP was not diminished by tetrodotoxin indicating that ATP was not likely released as a result of propagated action potentials in nerves. Because contractions persisted in the presence of tetrodotoxin, it is possible that the ATP might have been released as a result of direct electrical stimulation of the muscle. These results do not support the idea that ATP is released as a neurotransmitter in the rabbit bladder.

scholarly journals PapRIV, a BV-2 microglial cell activating quorum sensing peptide

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yorick Janssens ◽  
Nathan Debunne ◽  
Anton De Spiegeleer ◽  
Evelien Wynendaele ◽  
Marta Planas ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Cell Model ◽  
Dependent Manner ◽  
Communication Signals ◽  
Gram Positive Bacteria ◽  
A Cell ◽  
Gastro Intestinal Tract

AbstractQuorum sensing peptides (QSPs) are bacterial peptides produced by Gram-positive bacteria to communicate with their peers in a cell-density dependent manner. These peptides do not only act as interbacterial communication signals, but can also have effects on the host. Compelling evidence demonstrates the presence of a gut-brain axis and more specifically, the role of the gut microbiota in microglial functioning. The aim of this study is to investigate microglial activating properties of a selected QSP (PapRIV) which is produced by Bacillus cereus species. PapRIV showed in vitro activating properties of BV-2 microglia cells and was able to cross the in vitro Caco-2 cell model and reach the brain. In vivo peptide presence was also demonstrated in mouse plasma. The peptide caused induction of IL-6, TNFα and ROS expression and increased the fraction of ameboid BV-2 microglia cells in an NF-κB dependent manner. Different metabolites were identified in serum, of which the main metabolite still remained active. PapRIV is thus able to cross the gastro-intestinal tract and the blood–brain barrier and shows in vitro activating properties in BV-2 microglia cells, hereby indicating a potential role of this quorum sensing peptide in gut-brain interaction.

Role of enteric glial cells in the toxicity of phycotoxins: Investigation with a tri-culture intestinal cell model

2021 ◽  
Vol 351 ◽  
pp. 89-98
Author(s):  
Océane Reale ◽  
Dorina Bodi ◽  
Antoine Huguet ◽  
Valérie Fessard
Keyword(s):  
Glial Cells ◽  
Cell Model ◽  
Intestinal Cell ◽  
Enteric Glial Cells
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