scholarly journals Kinetic analysis of single sodium channels from canine cardiac Purkinje cells.

1990 ◽  
Vol 95 (3) ◽  
pp. 411-437 ◽  
Author(s):  
B E Scanley ◽  
D A Hanck ◽  
T Chay ◽  
H A Fozzard

Single sodium channel events were recorded from cell-attached patches on single canine cardiac Purkinje cells at 10-13 degrees C. Data from four patches containing two to four channels and one patch with one channel were selected for quantitative analysis. The channels showed prominent reopening behavior at voltages near threshold, and the number of reopenings declined steeply with depolarization. Mean channel open time was a biphasic function of voltage with the maximum value (1-1.5 ms) occurring between -50 and -40 mV and lower values at more and at less hyperpolarized levels. Inactivation without opening was also prominent near threshold, and this occurrence also declined with depolarization. The waiting time distributions and the probability of being open showed voltage and time dependence as expected from whole-cell current studies. The results were analyzed in terms of a five-state Markovian kinetic model using both histogram analysis and a maximum likelihood method to estimate kinetic parameters. The kinetic parameters of the model fits were similar to those of GH3 pituitary cells (Horn, R., and C. A. Vandenberg. 1984. Journal of General Physiology. 84:505-534) and N1E115 neuroblastoma cells (Aldrich, R. W., and C. F. Stevens. Journal of Neuroscience. 7:418-431). Both histogram and maximum likelihood analysis implied that much of the voltage dependence of cardiac Na current is in its activation behavior, with inactivation showing modest voltage dependence.

1989 ◽  
Vol 256 (5) ◽  
pp. H1478-H1492 ◽  
Author(s):  
Y. Hirano ◽  
H. A. Fozzard ◽  
C. T. January

Two types of Ca2+ currents were recorded in single dialyzed canine cardiac Purkinje cells using a whole cell voltage clamp technique. T-type current was easily separated from L-type current, because its voltage dependence of inactivation and activation was more negative and it decayed rapidly. L-type current was available at more depolarized holding potentials, activated at more positive voltages, and decayed slowly. In 2 mM extracellular Ca2+ concentration [( Ca]o), the average peak T- and L-type current density was 1.70 and 2.87 pA/pF, respectively. T-type current was relatively insensitive to modification by Ca2+, nifedipine, Cd2+, BAY K 8644, or isoproterenol. T-type current was more sensitive to block by Ni2+ and amiloride. Replacement of Ca2+ by Ba2+ or Sr2+ did not increase T-type current. Changes in the Ca2+ or Ba2+ concentration caused parallel shifts in the voltage dependence of several kinetic parameters for L- and T-type current. In 2 mM [Ca]o, the V1/2 (Boltzmann fit) for inactivation of T-type current was -68 mV with a slope of 3.9, and for L-type current the V1/2 was -31 mV with a slope of 5.5. Recovery from inactivation of L- and T-type current was voltage dependent, and for similar conditions L-type current recovered from inactivation more rapidly than T-type current. These findings show that T- and L-type currents are large in cardiac Purkinje cells, and they can easily be separated by their voltage, kinetic, and pharmacological differences. Both may have important physiological roles.


AIChE Journal ◽  
2004 ◽  
Vol 50 (6) ◽  
pp. 1260-1272 ◽  
Author(s):  
Ali Habibi ◽  
Ebrahim Vasheghani-Farahani

2001 ◽  
Vol 280 (3) ◽  
pp. H1075-H1080 ◽  
Author(s):  
Wei Han ◽  
Zhiguo Wang ◽  
Stanley Nattel

Although cardiac Purkinje cells (PCs) are believed to be the source of early afterdepolarizations generating ventricular tachyarrhythmias in long Q-T syndromes (LQTS), the ionic determinants of PC repolarization are incompletely known. To evaluate the role of the slow delayed rectifier current ( I Ks) in PC repolarization, we studied PCs from canine ventricular false tendons with whole cell patch clamp (37°C). Typical I Ks voltage- and time-dependent properties were noted. Isoproterenol enhanced I Ks in a concentration-dependent fashion (EC50 ∼ 30 nM), negatively shifted I Ks activation voltage dependence, and accelerated I Ks activation. Block of I Ks with 293B did not alter PC action potential duration (APD) in the absence of isoproterenol; however, in the presence of isoproterenol, 293B significantly prolonged APD. We conclude that, without β-adrenergic stimulation, I Ks contributes little to PC repolarization; however, β-adrenergic stimulation increases the contribution of I Ks by increasing current amplitude, accelerating I Ks activation, and shifting activation voltage toward the PC plateau voltage range. I Ks may therefore provide an important “braking” function to limit PC APD prolongation in the presence of β-adrenergic stimulation.


1992 ◽  
Vol 262 (4) ◽  
pp. H1197-H1207 ◽  
Author(s):  
D. A. Hanck ◽  
M. F. Sheets

The spontaneous hyperpolarizing shift in Na+ channel kinetics that occurs during a series of voltage-clamp recordings was characterized in single canine cardiac Purkinje cells at 10-13.5 degrees C. The change in the half-point of voltage-dependent availability, in the half-point of peak conductance, in the voltage dependence of deactivation and time to peak Na+ channel current (INa), and in the time constants of INa decay in response to step depolarizations were examined. The half points of availability and conductance shifted similarly, -0.41 +/- 0.13 and -0.47 +/- 0.19 mV/min, respectively (n = 14). These were directly correlated (slope 1.14 +/- 0.06, R2 = 0.81) with conductance shifting on average only -0.05 mV/min faster than availability. The deactivation time constant-voltage relationship shifted similarly to availability and conductance. Tail current decay time constants predicted the voltage dependence of the open to closed transition to be 0.9e-. Time to peak INa in response to step depolarizations changed e-fold for 25 mV but plateaued at positive potentials (531 microseconds, n = 22). INa decay was multiexponential between -40 and 80 mV. Decay time constants changed little as a function of voltage at positive potentials. The contribution of the second time constant to decay amplitude was 15-20% over the entire voltage range. Time to peak INa shifted in a curvilinear fashion, changing less late in an experiment. We conclude that the channel-voltage sensor responds to a changing fraction of the applied voltage during an experiment, producing similar rates of shift of voltage-dependent availability, conductance, and deactivation time constants.


Author(s):  
Maristella De Araújo Carvalho Sousa ◽  
Raymundo Paraná ◽  
Luis Jesuino De Oliveira Andrade

Background: Thyroid-stimulating hormone (TSH) is a member of the vertebrate glycoprotein hormone family [1]. It’s secreted from pituitary cells as heterodimers composed of an alpha and a beta- subunit. The thyrotrophic cells that secrete TSH are preferentially located in the anteromedial and anterolateral portions of the pituitary. Objective: We performed a phylogenetic analysis of the TSH, and phylogram of the maximum likelihood relations between TSH coding sequences of five representative species. Methods: We extracted the available DNA and protein sequences for TSH from the NCBI databank. Searched for regions presenting sequence similarities to the constituent domains of TSH – alpha and beta-subunits - with the Blastall command ftp://ftp.ncbi.nlm.nih.gov/blast/db/ website, pairs of sequences were compared on the basis of their global alignment with the Myers & Millers algorithm manpages.ubuntu. com/manpages/karmic/man1, and the phylogenetic reconstructions were performed online by using a maximum likelihood method with PhyMyL 3.0 software on the website file (http://www.phylogeny.fr/). Results: The comparison of the phylogenetic trees that we obtained compared with those studies previously published revealed similar subclusters with high protein homology. Conclusion: This study demonstrates that human TSH is structurally related to TSH of the species analysed, Bos taurus, Mus musculus, Canis lupus familiaris, and Cyprinus carpio, respectively.


Author(s):  
Anggis Sagitarisman ◽  
Aceng Komarudin Mutaqin

AbstractCar manufacturers in Indonesia need to determine reasonable warranty costs that do not burden companies or consumers. Several statistical approaches have been developed to analyze warranty costs. One of them is the Gertsbakh-Kordonsky method which reduces the two-dimensional warranty problem to one dimensional. In this research, we apply the Gertsbakh-Kordonsky method to estimate the warranty cost for car type A in XYZ company. The one-dimensional data will be tested using the Kolmogorov-Smirnov to determine its distribution and the parameter of distribution will be estimated using the maximum likelihood method. There are three approaches to estimate the parameter of the distribution. The difference between these three approaches is in the calculation of mileage for units that do not claim within the warranty period. In the application, we use claim data for the car type A. The data exploration indicates the failure of car type A is mostly due to the age of the vehicle. The Kolmogorov-Smirnov shows that the most appropriate distribution for the claim data is the three-parameter Weibull. Meanwhile, the estimated using the Gertsbakh-Kordonsky method shows that the warranty costs for car type A are around 3.54% from the selling price of this car unit without warranty i.e. around Rp. 4,248,000 per unit.Keywords: warranty costs; the Gertsbakh-Kordonsky method; maximum likelihood estimation; Kolmogorov-Smirnov test.                                   AbstrakPerusahaan produsen mobil di Indonesia perlu menentukan biaya garansi yang bersifat wajar tidak memberatkan perusahaan maupun konsumen. Beberapa pendekatan statistik telah dikembangkan untuk menganalisis biaya garansi. Salah satunya adalah metode Gertsbakh-Kordonsky yang mereduksi masalah garansi dua dimensi menjadi satu dimensi. Pada penelitian ini, metode Gertsbakh-Kordonsky akan digunakan untuk mengestimasi biaya garansi untuk mobil tipe A pada perusahaan XYZ. Data satu dimensi hasil reduksi diuji kecocokan distribusinya menggunakan uji kecocokan Kolmogorov-Smirnov dan taksiran parameter distribusinya menggunakan metode penaksir kemungkinan maksimum. Ada tiga pendekatan yang digunakan untuk menaksir parameter distribusi. Perbedaan dari ketiga pendekatan tersebut terletak pada perhitungan jarak tempuh untuk unit yang tidak melakukan klaim dalam periode garansi. Sebagai bahan aplikasi, kami menggunakan data klaim unit mobil tipe A. Hasil eksplorasi data menunjukkan bahwa kegagalan mobil tipe A lebih banyak disebabkan karena faktor usia kendaraan. Hasil uji kecocokan distribusi untuk data hasil reduksi menunjukkan bahwa distribusi yang cocok adalah distribusi Weibull 3-parameter. Sementara itu, hasil perhitungan taksiran biaya garansi menunjukan bahwa taksiran biaya garansi untuk unit mobil tipe A sekitar 3,54% dari harga jual unit mobil tipe A tanpa garansi, atau sekitar Rp. 4.248.000,- per unit.Kata Kunci: biaya garansi; metode Gertsbakh-Kordonsky; penaksiran kemungkinan maksimum; uji Kolmogorov-Smirnov.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Guanglei Xu ◽  
William S. Oates

AbstractRestricted Boltzmann Machines (RBMs) have been proposed for developing neural networks for a variety of unsupervised machine learning applications such as image recognition, drug discovery, and materials design. The Boltzmann probability distribution is used as a model to identify network parameters by optimizing the likelihood of predicting an output given hidden states trained on available data. Training such networks often requires sampling over a large probability space that must be approximated during gradient based optimization. Quantum annealing has been proposed as a means to search this space more efficiently which has been experimentally investigated on D-Wave hardware. D-Wave implementation requires selection of an effective inverse temperature or hyperparameter ($$\beta $$ β ) within the Boltzmann distribution which can strongly influence optimization. Here, we show how this parameter can be estimated as a hyperparameter applied to D-Wave hardware during neural network training by maximizing the likelihood or minimizing the Shannon entropy. We find both methods improve training RBMs based upon D-Wave hardware experimental validation on an image recognition problem. Neural network image reconstruction errors are evaluated using Bayesian uncertainty analysis which illustrate more than an order magnitude lower image reconstruction error using the maximum likelihood over manually optimizing the hyperparameter. The maximum likelihood method is also shown to out-perform minimizing the Shannon entropy for image reconstruction.


Author(s):  
Vijitashwa Pandey ◽  
Deborah Thurston

Design for disassembly and reuse focuses on developing methods to minimize difficulty in disassembly for maintenance or reuse. These methods can gain substantially if the relationship between component attributes (material mix, ease of disassembly etc.) and their likelihood of reuse or disposal is understood. For products already in the marketplace, a feedback approach that evaluates willingness of manufacturers or customers (decision makers) to reuse a component can reveal how attributes of a component affect reuse decisions. This paper introduces some metrics and combines them with ones proposed in literature into a measure that captures the overall value of a decision made by the decision makers. The premise is that the decision makers would choose a decision that has the maximum value. Four decisions are considered regarding a component’s fate after recovery ranging from direct reuse to disposal. A method on the lines of discrete choice theory is utilized that uses maximum likelihood estimates to determine the parameters that define the value function. The maximum likelihood method can take inputs from actual decisions made by the decision makers to assess the value function. This function can be used to determine the likelihood that the component takes a certain path (one of the four decisions), taking as input its attributes, which can facilitate long range planning and also help determine ways reuse decisions can be influenced.


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