Stochastic Hodgkin-Huxley Equations with Colored Noise Terms in the Conductances

2013 ◽  
Vol 25 (1) ◽  
pp. 46-74 ◽  
Author(s):  
Marifi Güler
Keyword(s):  
Colored Noise ◽  
Open Channel ◽  
Small Cells ◽  
Spontaneous Firing ◽  
Spike Generation ◽  
Membrane Area ◽  
Transmembrane Voltage ◽  
Cross Correlations ◽  
Firing Efficiency ◽  
Voltage Gated Ion Channels

The excitability of cells is facilitated by voltage-gated ion channels. These channels accommodate a multiple number of gates individually. The possible impact of that gate multiplicity on the cell's function, specifically when the membrane area is of limited size, was investigated in the author's prior work (Güler, 2011 ). There, it was found that a nontrivially persistent correlation takes place between the transmembrane voltage fluctuations (also between the fluctuations in the gating variables) and the component of open channel fluctuations attributed to the gate multiplicity. This nontrivial phenomenon was found to be playing a major augmentative role for the elevation of excitability and spontaneous firing in small cells. In addition, the same phenomenon was found to be enhancing spike coherence significantly. Here we extend Fox and Lu's ( 1994 ) stochastic Hodgkin-Huxley equations by incorporating colored noise terms into the conductances there to obtain a formalism capable of capturing the addressed cross-correlations. Statistics of spike generation, spike coherence, firing efficiency, latency, and jitter from the articulated set of equations are found to be highly accurate in comparison with the corresponding statistics from the exact microscopic Markov simulations. This way, it is demonstrated vividly that our formulation overcomes the inherent inadequacy of the Fox and Lu equations. Finally, a recently proposed diffusion approximation method (Linaro, Storace, & Giugliano, 2011 ) is taken into consideration, and a discussion on its character is pursued.

scholarly journals An investigation of the coefficient of variation using voltage clamps techniques

2015 ◽  
Vol 4 (4) ◽  
pp. 364
Author(s):  
Ahmed Mahmood Khudhur ◽  
Ahmed N Abdalla ◽  
Jasni Mohamad Zain ◽  
Hai Tao
Keyword(s):  
Ion Channel ◽  
Coefficient Of Variation ◽  
Cross Correlation ◽  
Open Channel ◽  
Dynamical Behavior ◽  
Channel Noise ◽  
Spontaneous Firing ◽  
Voltage Clamps ◽  
Transmembrane Voltage ◽  
Ion Channel Noise

<p class="MsoNormal" style="text-align: justify; text-justify: inter-ideograph;"><span style="font-size: 10.0pt;">In recent years, it has been argued and experimentally shown that ion channel noise in neurons can have profound effects on the neuron’s dynamical behavior. Most profoundly, ion channel noise was seen to be able to cause spontaneous firing and stochastic resonance. It has been recently found that a non-trivially persistent cross correlation takes place between the transmembrane voltage fluctuations and the component of open channel fluctuations attributed to gate multiplicity. This non-trivial phenomenon was found to play a major augmentative role for the elevation of excitability and spontaneous firing in the small size cell. In addition, the same phenomenon was found to significantly enhance the spike coherence. In this paper, statistics of the coefficient of variation, to be obtained from the colored stochastic Hodgkin-Huxley equations using voltage clamps techniqueswill be studied. The simulation result shows the coefficient of variation; enhance the agreement with the microscopeinthe case of the noisy currents.</span></p>

scholarly journals Reversal of HCN Channel Voltage Dependence via Bridging of the S4–S5 Linker and Post-S6

2006 ◽  
Vol 128 (3) ◽  
pp. 273-282 ◽  
Author(s):  
David L. Prole ◽  
Gary Yellen
Keyword(s):  
Voltage Dependence ◽  
Disulfide Bridges ◽  
Hcn Channel ◽  
Channel Activation ◽  
Transmembrane Voltage ◽  
Pacemaker Channel ◽  
Positive Voltage ◽  
Close Proximity ◽  
Inactivation Process ◽  
Voltage Gated Ion Channels

Voltage-gated ion channels possess charged domains that move in response to changes in transmembrane voltage. How this movement is transduced into gating of the channel pore is largely unknown. Here we show directly that two functionally important regions of the spHCN1 pacemaker channel, the S4–S5 linker and the C-linker, come into close proximity during gating. Cross-linking these regions with high-affinity metal bridges or disulfide bridges dramatically alters channel gating in the absence of cAMP; after modification the polarity of voltage dependence is reversed. Instead of being closed at positive voltage and activating with hyperpolarization, modified channels are closed at negative voltage and activate with depolarization. Mechanistically, this reversal of voltage dependence occurs as a result of selectively eliminating channel deactivation, while retaining an existing inactivation process. Bridging also alters channel activation by cAMP, showing that interaction of these two regions can also affect the efficacy of physiological ligands.

scholarly journals Stargazin and cornichon-3 relieve polyamine block of AMPA receptors by enhancing blocker permeation

2017 ◽  
Vol 150 (1) ◽  
pp. 67-82 ◽  
Author(s):  
Patricia M.G.E. Brown ◽  
Hugo McGuire ◽  
Derek Bowie
Keyword(s):  
Ampa Receptors ◽  
Open Channel ◽  
Underlying Mechanism ◽  
Ionotropic Glutamate Receptors ◽  
Mammalian Brain ◽  
Channel Block ◽  
Glutamatergic Synapses ◽  
Modified Model ◽  
Auxiliary Subunits ◽  
Voltage Gated Ion Channels

Most ligand- and voltage-gated ion channels assemble as signaling complexes consisting of pore-forming and auxiliary subunits. In the mammalian brain, AMPA-type ionotropic glutamate receptors (AMPARs) coassemble with several families of auxiliary subunits that regulate channel gating as well as ion channel block and permeation. Previous work has shown that auxiliary proteins stargazin (or γ2) and cornichon-3 (CNIH-3) attenuate the cytoplasmic polyamine channel block of AMPARs, although the underlying mechanism has yet to be established. Here, we show that γ2 and CNIH-3 relieve channel block by enhancing the rate of blocker permeation. Surprisingly, the relative permeability of the polyamine spermine (Spm) through the pore of the AMPAR-γ2 or -CNIH-3 complexes is considerably more than AMPARs expressed alone. Spm permeability is comparable to that of Na+ for the GluA2-γ2 complex and four times greater than Na+ with GluA2 + CNIH-3. A modified model of permeant channel block fully accounts for both the voltage- and time-dependent nature of Spm block. Estimates of block rate constants reveal that auxiliary subunits do not attenuate block by shifting the location of the block site within the membrane electric field, and they do not affect the blocker’s ability to reach it. Instead, γ2 and CNIH-3 relieve channel block by facilitating the blocker’s exit rates from the open channel. From a physiological perspective, the relief of channel block exerted by γ2 and CNIH-3 ensures that there is unfettered signaling by AMPARs at glutamatergic synapses. Moreover, the pronounced ability of AMPARs to transport polyamines may have an unexpected role in regulating cellular polyamine levels.

Computer simulation of group Ia EPSPs using morphologically realistic models of cat alpha-motoneurons

1990 ◽  
Vol 64 (2) ◽  
pp. 648-660 ◽  
Author(s):  
I. Segev ◽  
J. W. Fleshman ◽  
R. E. Burke
Keyword(s):  
Input Resistance ◽  
The Other ◽  
Triceps Surae ◽  
Synaptic Current ◽  
Membrane Area ◽  
Synaptic Inputs ◽  
Transmembrane Voltage ◽  
Activation Times ◽  
Total Membrane ◽  
Temporal Dispersion

1. Morphological and electrophysiological data on the electrotonic structure of six triceps surae alpha-motoneurons and on the number and location of 202 Group Ia synapses making contact with ankle extensor motoneurons, previously obtained in this laboratory, were used to construct computer models to examine the generation of composite monosynaptic Group Ia excitatory postsynaptic potentials (EPSPs). 2. A total of 300 active synapses, each generating conductance transients based on voltage-clamp data and having activation times temporally dispersed (range approximately 1.3 ms) according to the conduction velocity profile of Group Ia-afferents, were used to generate composite EPSPs. 3. The shape indexes (foot-to-peak rise times and half widths) of simulated EPSPs matched those of experimentally observed Ia EPSPs reasonably well, although the rise times were, on average, approximately 0.25 ms longer in the simulated EPSPs. This may indicate that the effective temporal dispersion of actual Group Ia monosynaptic EPSPs is less than that the temporal asynchrony used in the simulations. 4. The peak amplitudes of simulated composite EPSPs (6-14 mV), as well as EPSPs produced by single somatic synapses (80-300 microV), were comparable to those found in experimental data. 5. Simulated EPSPs in motoneuron models with two forms of nonuniform Rm distribution ("step" increase from low values of Rm on the soma to much higher but uniform values in the dendrites, versus gradual monotonic "sigmoidal" increases from soma to distal dendrites) were similar in shape and amplitude. This prevented choosing one or the other Rm model as more "correct." 6. Transmembrane voltages at synaptic sites in motoneuron dendrites during generation of composite Ia EPSPs had peak amplitudes less than twice those of the somatic EPSP. The amount of nonlinearity during EPSP production was assessed by making the delivery of synaptic current independent of the local transmembrane voltage. This non-linearity was modest (less than 10%) during composite EPSP generation, consistent with previous experimental evidence. 7. The local voltages produced in various parts of different dendrites during composite EPSP generation depended on the number and location of active synapses and on the electrotonic structure of the particular dendrite. The results show that dendrites that project in different directions away from the motoneuron soma could, in principle, exhibit different degrees of interaction between Ia and other synaptic inputs. 8. Although produced by the same number of active synapses, the simulated composite Ia EPSPs varied over a two-fold range of peak amplitude in relation to motor-unit type, cell input resistance, and cell size (total membrane area).(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals A new approach for investigating the response of lipid membranes to electrocompression by coupling droplet mechanics and membrane biophysics

2019 ◽  
Vol 16 (161) ◽  
pp. 20190652 ◽  
Author(s):  
Joyce El-Beyrouthy ◽  
Michelle M. Makhoul-Mansour ◽  
Graham Taylor ◽  
Stephen A. Sarles ◽  
Eric C. Freeman
Keyword(s):  
Contact Angle ◽  
Lipid Membranes ◽  
Bilayer Membrane ◽  
Residual Energy ◽  
Membrane Biophysics ◽  
Membrane Properties ◽  
Lipid Monolayer ◽  
Membrane Tension ◽  
Membrane Area ◽  
Transmembrane Voltage

A new method for quantifying lipid–lipid interactions within biomimetic membranes undergoing electrocompression is demonstrated by coupling droplet mechanics and membrane biophysics. The membrane properties are varied by altering the lipid packing through the introduction of cholesterol. Pendant drop tensiometry is used to measure the lipid monolayer tension at an oil–water interface. Next, two lipid-coated aqueous droplets are manipulated into contact to form a bilayer membrane at their adhered interface. The droplet geometries are captured from two angles to provide accurate measurements of both the membrane area and the contact angle between the adhered droplets. Combining the monolayer tension and contact angle measurements enables estimations of the membrane tension with respect to lipid composition. Then, the membrane is electromechanically compressed using a transmembrane voltage. Electrostatic pressure, membrane tension and the work necessary for bilayer thinning are tracked, and a model is proposed to capture the mechanics of membrane compression. The results highlight that a previously unaccounted for energetic term is produced during compression, potentially reflecting changes in the lateral membrane structure. This residual energy is eliminated in cases with cholesterol mole fractions of 0.2 and higher, suggesting that cholesterol diminishes these adjustments.

S4 Charges Move Close to Residues in the Pore Domain during Activation in a K Channel

2001 ◽  
Vol 118 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Fredrik Elinder ◽  
Roope Männikkö ◽  
H. Peter Larsson
Keyword(s):  
Close Approach ◽  
Voltage Sensor ◽  
K Channel ◽  
Slow Inactivation ◽  
Transmembrane Voltage ◽  
Activated State ◽  
Ion Conducting ◽  
Voltage Gated Ion Channels ◽  
Modification Rate ◽  
Positively Charged

Voltage-gated ion channels respond to changes in the transmembrane voltage by opening or closing their ion conducting pore. The positively charged fourth transmembrane segment (S4) has been identified as the main voltage sensor, but the mechanisms of coupling between the voltage sensor and the gates are still unknown. Obtaining information about the location and the exact motion of S4 is an important step toward an understanding of these coupling mechanisms. In previous studies we have shown that the extracellular end of S4 is located close to segment 5 (S5). The purpose of the present study is to estimate the location of S4 charges in both resting and activated states. We measured the modification rates by differently charged methanethiosulfonate regents of two residues in the extracellular end of S5 in the Shaker K channel (418C and 419C). When S4 moves to its activated state, the modification rate by the negatively charged sodium (2-sulfonatoethyl) methanethiosulfonate (MTSES−) increases significantly more than the modification rate by the positively charged [2-(trimethylammonium)ethyl] methanethiosulfonate, bromide (MTSET+). This indicates that the positive S4 charges are moving close to 418C and 419C in S5 during activation. Neutralization of the most external charge of S4 (R362), shows that R362 in its activated state electrostatically affects the environment at 418C by 19 mV. In contrast, R362 in its resting state has no effect on 418C. This suggests that, during activation of the channel, R362 moves from a position far away (&gt;20 Å) to a position close (8 Å) to 418C. Despite its close approach to E418, a residue shown to be important in slow inactivation, R362 has no effect on slow inactivation or the recovery from slow inactivation. This refutes previous models for slow inactivation with an electrostatic S4-to-gate coupling. Instead, we propose a model with an allosteric mechanism for the S4-to-gate coupling.

scholarly journals Thermal and Oxygen Flight Sensitivity in Ageing Drosophila melanogaster Flies: Links to Rapamycin-Induced Cell Size Changes

Biology ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 861
Author(s):  
Ewa Szlachcic ◽  
Marcin Czarnoleski
Keyword(s):  
Drosophila Melanogaster ◽  
Cell Membrane ◽  
Cell Size ◽  
Large Cell ◽  
Small Cell ◽  
Small Cells ◽  
Cell Phenotype ◽  
Membrane Area ◽  
Flying Insects ◽  
Oxygen Conditions

Ectotherms can become physiologically challenged when performing oxygen-demanding activities (e.g., flight) across differing environmental conditions, specifically temperature and oxygen levels. Achieving a balance between oxygen supply and demand can also depend on the cellular composition of organs, which either evolves or changes plastically in nature; however, this hypothesis has rarely been examined, especially in tracheated flying insects. The relatively large cell membrane area of small cells should increase the rates of oxygen and nutrient fluxes in cells; however, it does also increase the costs of cell membrane maintenance. To address the effects of cell size on flying insects, we measured the wing-beat frequency in two cell-size phenotypes of Drosophila melanogaster when flies were exposed to two temperatures (warm/hot) combined with two oxygen conditions (normoxia/hypoxia). The cell-size phenotypes were induced by rearing 15 isolines on either standard food (large cells) or rapamycin-enriched food (small cells). Rapamycin supplementation (downregulation of TOR activity) produced smaller flies with smaller wing epidermal cells. Flies generally flapped their wings at a slower rate in cooler (warm treatment) and less-oxygenated (hypoxia) conditions, but the small-cell-phenotype flies were less prone to oxygen limitation than the large-cell-phenotype flies and did not respond to the different oxygen conditions under the warm treatment. We suggest that ectotherms with small-cell life strategies can maintain physiologically demanding activities (e.g., flight) when challenged by oxygen-poor conditions, but this advantage may depend on the correspondence among body temperatures, acclimation temperatures and physiological thermal limits.

Electrophysiologic Evidence for Involvement of Acetylcholine as a Neurotransmitter in the Lateral Vestibular Nucleus

1981 ◽  
Vol 89 (6) ◽  
pp. 1025-1029 ◽  
Author(s):  
Juichi Ito ◽  
Izuru Matsuoka ◽  
Masashi Sasa ◽  
Sakae Fujimoto ◽  
Shuji Takaori
Keyword(s):  
Nerve Stimulation ◽  
Vestibular Nucleus ◽  
Vestibular Nerve ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Spontaneous Firing ◽  
Lateral Vestibular Nucleus ◽  
Spike Generation

Monosynaptic spike generation of lateral vestibular nucleus (LVN) neurons with vestibular nerve stimulation in cats was inhibited by microiontophoretic atropine and gamma-aminobutyric acid (GABA). Spontaneous firing of the LVN monosynaptic neuron was increased by iontophoretic acetylcholine and glutamate. Atropine inhibited acetylcholine-induced firing without affecting glutamate-induced firing, while GABA blocked spike generation produced by acetylcholine and glutamate. Acetylcholine probably plays a role in transmission from the vestibular nerve to the LVN monosynaptic neurons.

Comparison of Choriocarcinoma and Normal Placenta

1971 ◽  
Vol 29 ◽  
pp. 324-325
Author(s):  
John C. Garancis ◽  
Roland A. Pattillo ◽  
Robert O. Hussa ◽  
Jon V. Straumfjord
Keyword(s):  
Cell Lines ◽  
Small Cells ◽  
Tissue Cultures ◽  
Glycogen Depletion ◽  
Cell Surfaces ◽  
Intercellular Spaces ◽  
Concomitant Increase ◽  
Gestational Choriocarcinoma ◽  
Cytoplasmic Glycogen ◽  
Normal Placenta

Two different cell lines (Be-Wo and Jar) of human gestational choriocarcinoma have been maintained in continuous tissue culture for a period of four and two years respectively without losing the ability to elaborate human chorionic gonadotropin (HCG). Tissue cultures, as revealed by electron microscopy, consisted of small cells with single nuclei. In some instances cell surfaces were provided with microvilli but more often the intercellular spaces were narrow and bridged by desmosomes. However, syncytium was not formed. Endoplasmic reticulum (ER) was poorly developed in both cell lines, except in some Be-Wo cells it was prominent. Golgi complex, lysosomes and numerous free ribosomes, as well as excessive cytoplasmic glycogen, were present in all cells (Fig. 1). Glycogen depletion and concomitant increase of ER were observed in many cells following a single dose of 10 ugm/ml of adrenalin added to medium (Fig. 2).

Sign in / Sign up

Export Citation Format

Share Document