scholarly journals A population density and moment-based approach to modeling domain Ca-mediated inactivation of L-type Ca channels

2015 ◽  
Author(s):  
Xiao Wang ◽  
Kiah Hardcastle ◽  
Seth H Weinberg ◽  
Gregory D Smith
Keyword(s):  
Population Density ◽  
Time Constant ◽  
Traditional Approach ◽  
Markov Chain Model ◽  
Order Moment ◽  
Chain Model ◽  
Ca Channel ◽  
Ca Channels ◽  
Moment Equations ◽  
Whole Cell

We present a population density and moment-based description of the stochastic dynamics of domain Ca-mediated inactivation of L-type Ca channels. Our approach accounts for the effect of heterogeneity of local Ca signals on whole cell Ca currents; however, in contrast with prior work, e.g., Sherman et al. (1990), we do not assume that Ca domain formation and collapse are fast compared to channel gating. We demonstrate the population density and moment-based modeling approaches using a 12-state Markov chain model of an L-type Ca channel introduced by Greenstein and Winslow (2002). Simulated whole cell voltage clamp responses yield an inactivation function for the whole cell Ca current that agrees with the traditional approach when domain dynamics are fast. We analyze the voltage-dependence of Ca inactivation that may occur via slow heterogeneous domains. Next, we find that when channel permeability is held constant, Ca-mediated inactivation of L-type channel increases as the domain time constant increases, because a slow domain collapse rate leads to increased mean domain [Ca] near open channels; conversely, when the maximum domain [Ca] is held constant, inactivation decreases as the domain time constant increases. Comparison of simulation results using population densities and moment equations confirms the computational efficiency of the moment-based approach, and enables the validation of two distinct methods of truncating and closing the open system of moment equations. In general, a slow domain time constant requires higher order moment truncation for agreement between moment-based and population density simulations.

scholarly journals Calcium-activated potassium channels in resting and activated human T lymphocytes. Expression levels, calcium dependence, ion selectivity, and pharmacology.

1993 ◽  
Vol 102 (4) ◽  
pp. 601-630 ◽  
Author(s):  
S Grissmer ◽  
A N Nguyen ◽  
M D Cahalan
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Ion Selectivity ◽  
Hill Coefficient ◽  
Ca Channel ◽  
Ca Channels ◽  
Patch Clamp Recording ◽  
Open Probability ◽  
Whole Cell ◽  
Unitary Conductance

Ca(2+)-activated K+[K(Ca)] channels in resting and activated human peripheral blood T lymphocytes were characterized using simultaneous patch-clamp recording and fura-2 monitoring of cytosolic Ca2+ concentration, [Ca2+]i. Whole-cell experiments, using EGTA-buffered pipette solutions to raise [Ca2+]i to 1 microM, revealed a 25-fold increase in the number of conducting K(Ca) channels per cell, from an average of 20 in resting T cells to > 500 channels per cell in T cell blasts after mitogenic activation. The opening of K(Ca) channels in both whole-cell and inside-out patch experiments was highly sensitive to [Ca2+]i (Hill coefficient of 4, with a midpoint of approximately 300 nM). At optimal [Ca2+]i, the open probability of a K(Ca) channel was 0.3-0.5. K(Ca) channels showed little or no voltage dependence from -100 to 0 mV. Single-channel I-V curves were linear with a unitary conductance of 11 pS in normal Ringer and exhibited modest inward rectification with a unitary conductance of approximately 35 pS in symmetrical 160 mM K+. Permeability ratios, relative to K+, determined from reversal potential measurements were: K+ (1.0) > Rb+ (0.96) > NH4+ (0.17) > Cs+ (0.07). Slope conductance ratios were: NH4+ (1.2) > K+ (1.0) > Rb+ (0.6) > Cs+ (0.10). Extracellular Cs+ or Ba2+ each induced voltage-dependent block of K(Ca) channels, with block increasing at hyperpolarizing potentials in a manner suggesting a site of block 75% across the membrane field from the outside. K(Ca) channels were blocked by tetraethylammonium (TEA) applied externally (Kd = 40 mM), but were unaffected by 10 mM TEA applied inside by pipette perfusion. K(Ca) channels were blocked by charybdotoxin (CTX) with a half-blocking dose of 3-4 nM, but were resistant to block by noxiustoxin (NTX) at 1-100 nM. Unlike K(Ca) channels in Jurkat T cells, the K(Ca) channels of normal resting or activated T cells were not blocked by apamin. We conclude that while K(Ca) and voltage-gated K+ channels in the same cells share similarities in ion permeation, Cs+ and Ba2+ block, and sensitivity to CTX, the underlying proteins differ in structural characteristics that determine channel gating and block by NTX and TEA.

scholarly journals Ca-activation kinetics modulate successive puff/spark amplitude, duration and inter-event-interval correlations in a Langevin model of stochastic Ca release

2015 ◽  
Author(s):  
Xiao Wang ◽  
Yan Hao ◽  
Seth H Weinberg ◽  
Gregory D Smith
Keyword(s):  
Markov Chain ◽  
Theoretical Analysis ◽  
Markov Chain Model ◽  
Release Site ◽  
Chain Model ◽  
Ca Channels ◽  
Activation Kinetics ◽  
Langevin Model ◽  
Physiological Range ◽  
Kinetics Of

Through theoretical analysis of the statistics of stochastic calcium (Ca) release (i.e., the amplitude, duration and inter-event interval of simulated Ca puffs and sparks), we show that a Langevin description of the collective gating of Ca channels may be a good approximation to the corresponding Markov chain model when the number of Ca channels per Ca release unit (CaRU) is in the physiological range. The Langevin description of stochastic Ca release facilitates our investigation of correlations between successive puff/spark amplitudes, durations and inter-spark intervals, and how such puff/spark statistics depend on the number of channels per release site and the kinetics of Ca-mediated inactivation of open channels. When Ca inactivation/de-inactivation rates are intermediate---i.e., the termination of Ca puff/sparks is caused by the recruitment of inactivated channels---the correlation between successive puff/spark amplitudes is negative, while the correlations between puff/spark amplitudes and the duration of the preceding or subsequent inter-spark interval are positive. These correlations are significantly reduced when inactivation/de-inactivation rates are extreme (slow or fast) and puff/sparks terminate via stochastic attrition.

scholarly journals Calcium channel selectivity for divalent and monovalent cations. Voltage and concentration dependence of single channel current in ventricular heart cells.

1986 ◽  
Vol 88 (3) ◽  
pp. 293-319 ◽  
Author(s):  
P Hess ◽  
J B Lansman ◽  
R W Tsien
Keyword(s):  
Binding Sites ◽  
Single Channel ◽  
Heart Cells ◽  
Ca Channel ◽  
Monovalent Cations ◽  
Ca Channels ◽  
Whole Cell ◽  
Double Occupancy ◽  
Monovalent Ions ◽  
Ca Ions

Single channel and whole cell recordings were used to study ion permeation through Ca channels in isolated ventricular heart cells of guinea pigs. We evaluated the permeability to various divalent and monovalent cations in two ways, by measuring either unitary current amplitude or reversal potential (Erev). According to whole cell measurements of Erev, the relative permeability sequence is Ca2+ greater than Sr2+ greater than Ba2+ for divalent ions; Mg2+ is not measurably permeant. Monovalent ions follow the sequence Li+ greater than Na+ greater than K+ greater than Cs+, and are much less permeant than the divalents. These whole cell measurements were supported by single channel recordings, which showed clear outward currents through single Ca channels at strong depolarizations, similar values of Erev, and similar inflections in the current-voltage relation near Erev. Information from Erev measurements stands in contrast to estimates of open channel flux or single channel conductance, which give the sequence Na+ (85 pS) greater than Li+ (45 pS) greater than Ba2+ (20 pS) greater than Ca2+ (9 pS) near 0 mV with 110-150 mM charge carrier. Thus, ions with a higher permeability, judged by Erev, have lower ion transfer rates. In another comparison, whole cell Na currents through Ca channels are halved by less than 2 microM [Ca]o, but greater than 10 mM [Ca]o is required to produce half-maximal unitary Ca current. All of these observations seem consistent with a recent hypothesis for the mechanism of Ca channel permeation, which proposes that: ions pass through the pore in single file, interacting with multiple binding sites along the way; selectivity is largely determined by ion affinity to the binding sites rather than by exclusion by a selectivity filter; occupancy by only one Ca ion is sufficient to block the pore's high conductance for monovalent ions like Na+; rapid permeation by Ca ions depends upon double occupancy, which only becomes significant at millimolar [Ca]o, because of electrostatic repulsion or some other interaction between ions; and once double occupancy occurs, the ion-ion interaction helps promote a quick exit of Ca ions from the pore into the cell.

Multiple kinetic effects of beta-adrenergic stimulation on single cardiac L-type Ca channels

1994 ◽  
Vol 266 (6) ◽  
pp. C1714-C1721 ◽  
Author(s):  
Y. Hirano ◽  
K. Suzuki ◽  
N. Yamawake ◽  
M. Hiraoka
Keyword(s):  
Time Constant ◽  
Kinetic Properties ◽  
Ca Channel ◽  
Ca Channels ◽  
Channel Activity ◽  
Adrenergic Stimulation ◽  
Open Probability ◽  
Beta Adrenergic ◽  
Open Time ◽  
Mode 2

During beta-adrenergic stimulation, several different mechanisms are known to modulate single cardiac L-type Ca channels, such as an increase in the proportion of nonblank sweeps (availability), graded changes in open and closed time constants, and potentiation of "mode 2" gating. To clarify the interrelationships of the above mechanisms in terms of "molecular modulation," we reevaluated the adenosine 3',5'-cyclic monophosphate-dependent increase in single cardiac Ca channel activity under conditions where all of the proposed mechanisms could take place. We observed considerable variations in the kinetic properties of basal channel activity among individual patches, presumably due to the diversity of intracellular metabolic conditions of individual myocytes. This made the contribution by each mechanism as described above variable from one patch to another. Increases in open probability during nonblank sweeps (associated with increased open time constant and/or promotion of mode 2 gating) were observed in patches were the increased nonblank rate was already established in the control state. In contrast with the report by D. T. Yue, S. Herzig, and E. Marban (Proc. Natl. Acad. Sci. USA 87: 753-757, 1990), graded changes in the open time constant could take place independently from the potentiation of mode 2 gating behavior. Our results suggest that the enhancement of cardiac L-type Ca channels during beta-stimulation involves multiple functional modulatory sites, which might be phosphorylated independently.

An Efficient Markov Chain Model for the Simulation of Heterogeneous Soil Structure

2004 ◽  
Vol 68 (2) ◽  
pp. 346 ◽  
Author(s):  
Keijan Wu ◽  
Naoise Nunan ◽  
John W. Crawford ◽  
Iain M. Young ◽  
Karl Ritz
Keyword(s):  
Markov Chain ◽  
Soil Structure ◽  
Markov Chain Model ◽  
Chain Model ◽  
Heterogeneous Soil

Data Mining Technique Applied To DNA Sequencing

2015 ◽  
Vol 2 (7) ◽  
pp. 18
Author(s):  
R. Jamuna
Keyword(s):  
Data Mining ◽  
Dna Methylation ◽  
Markov Chain ◽  
Human Genome ◽  
Transition Probabilities ◽  
Markov Chain Model ◽  
Effective Means ◽  
Cpg Islands ◽  
Chain Model ◽  
The Given

CpG islands (CGIs) play a vital role in genome analysis as genomic markers.  Identification of the CpG pair has contributed not only to the prediction of promoters but also to the understanding of the epigenetic causes of cancer. In the human genome [1] wherever the dinucleotides CG occurs the C nucleotide (cytosine) undergoes chemical modifications. There is a relatively high probability of this modification that mutates C into a T. For biologically important reasons the mutation modification process is suppressed in short stretches of the genome, such as ‘start’ regions. In these regions [2] predominant CpG dinucleotides are found than elsewhere. Such regions are called CpG islands. DNA methylation is an effective means by which gene expression is silenced. In normal cells, DNA methylation functions to prevent the expression of imprinted and inactive X chromosome genes. In cancerous cells, DNA methylation inactivates tumor-suppressor genes, as well as DNA repair genes, can disrupt cell-cycle regulation. The most current methods for identifying CGIs suffered from various limitations and involved a lot of human interventions. This paper gives an easy searching technique with data mining of Markov Chain in genes. Markov chain model has been applied to study the probability of occurrence of C-G pair in the given   gene sequence. Maximum Likelihood estimators for the transition probabilities for each model and analgously for the  model has been developed and log odds ratio that is calculated estimates the presence or absence of CpG is lands in the given gene which brings in many  facts for the cancer detection in human genome.

scholarly journals Performance Analysis of Synchronous Multi-Radio Multi-Link MAC Protocols in IEEE 802.11be Extremely High Throughput WLANs

2020 ◽  
Vol 11 (1) ◽  
pp. 317
Author(s):  
Taewon Song ◽  
Taeyoon Kim
Keyword(s):  
Ieee 802.11 ◽  
Markov Chain Model ◽  
Careful Consideration ◽  
Mac Protocols ◽  
Media Access Control ◽  
Chain Model ◽  
Distributed Coordination ◽  
Media Access ◽  
Medium Access ◽  
Coordination Function

The representative media access control (MAC) mechanism of IEEE 802.11 is a distributed coordination function (DCF), which operates based on carrier-sense multiple access with collision avoidance (CSMA/CA) with binary exponential backoff. The next amendment of IEEE 802.11 being developed for future Wi-Fi by the task group-be is called IEEE 802.11be, where the multi-link operation is mainly discussed when it comes to MAC layer operation. The multi-link operation discussed in IEEE 802.11be allows multi-link devices to establish multiple links and operate them simultaneously. Since the medium access on a link may affect the other links, and the conventional MAC mechanism has just taken account of a single link, the DCF should be used after careful consideration for multi-link operation. In this paper, we summarize the DCFs being reviewed to support the multi-radio multi-link operation in IEEE 802.11be and analyze their performance using the Markov chain model. Throughout the extensive performance evaluation, we summarize each MAC protocol’s pros and cons and discuss essential findings of the candidate MAC protocols.

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