scholarly journals Rapid characterisation of hERG channel kinetics II: temperature dependence

2019 ◽  
Author(s):  
Chon Lok Lei ◽  
Michael Clerx ◽  
Kylie A. Beattie ◽  
Dario Melgari ◽  
Jules C. Hancox ◽  
...  

ABSTRACTIon channel behaviour can depend strongly on temperature, with faster kinetics at physiological temperatures leading to considerable changes in currents relative to room temperature. These temperature-dependent changes in voltage-dependent ion channel kinetics (rates of opening, closing and inactivating) are commonly represented with Q10coefficients or an Eyring relationship. In this paper we assess the validity of these representations by characterising channel kinetics at multiple temperatures. We focus on the hERG channel, which is important in drug safety assessment and commonly screened at room temperature, so that results require extrapolation to physiological temperature. In Part I of this study we established a reliable method for high-throughput characterisation of hERG1a (Kv11.1) kinetics, using a 15 second information-rich optimised protocol. In this Part II, we use this protocol to study the temperature dependence of hERG kinetics using CHO cells over-expressing hERG1a on the Nanion SyncroPatch 384PE, a 384-well automated patch clamp platform, with temperature control. We characterise the temperature dependence of hERG gating by fitting the parameters of a mathematical model of hERG kinetics to data obtained at five distinct temperatures between 25 and 37 °C, and validate the models using different protocols. Our models reveal that activation is far more temperature sensitive than inactivation, and we observe that the temperature dependency of the kinetic parameters is not represented well by Q10coefficients: it broadly follows a generalised, but not the standardly-used, Eyring relationship. We also demonstrate that experimental estimations of Q10coefficients are protocol-dependent. Our results show that a direct fit using our 15 second protocol best represents hERG kinetics at any given temperature, and suggests that predictions from the Generalised Eyring theory may be preferentially used if no experimentally-derived data are available.Statement of SignificanceIon channel currents are highly sensitive to temperature changes. Yet because many experiments are performed more easily at room temperature, it is common to extrapolate findings to physiological temperatures through the use of Q10coefficients or Eyring rate theory. By applying short, information-rich protocols that we developed in Part I of this study we identify how kinetic parameters change over temperature. We find that the commonly-used Q10and Eyring formulations are incapable of describing the parameters’ temperature dependence, a more Generalised Eyring relationship works well, but remeasuring kinetics and refitting a model is optimal. The findings have implications for the accuracy of the many applications of Q10coefficients in electrophysiology, and suggest that care is needed to avoid misleading extrapolations in their many scientific and industrial pharmaceutical applications.

2019 ◽  
Vol 117 (12) ◽  
pp. 2455-2470 ◽  
Author(s):  
Chon Lok Lei ◽  
Michael Clerx ◽  
Kylie A. Beattie ◽  
Dario Melgari ◽  
Jules C. Hancox ◽  
...  

2021 ◽  
Author(s):  
Mara Almog ◽  
Nurit Degani-Katzav ◽  
Alon Korngreen

Like all biological and chemical reactions, ion channel kinetics are highly sensitive to changes in temperature. Therefore, it is prudent to investigate channel dynamics at physiological temperatures. However, most ion channel investigations are performed at room temperature due to practical considerations, such as recording stability and technical limitations. This problem is especially severe for the fast voltage-gated sodium channel, whose activation kinetics are faster than the time constant of the standard patch-clamp amplifier at physiological temperatures. Thus, biologically detailed simulations of the action potential generation evenly scale the kinetic models of voltage-gated channels acquired at room temperature. To quantitatively study voltage-gated sodium channels' temperature sensitivity, we recorded sodium currents from nucleated patches extracted from the rat's layer five neocortical pyramidal neurons at several temperatures from 13.5 to 30°C. We use these recordings to model the kinetics of the voltage-gated sodium channel as a function of temperature. We show that the temperature dependence of activation differs from that of inactivation. Furthermore, we show that the sustained current has a different temperature dependence than the fast current. Our kinetic and thermodynamic analysis of the current provided a numerical model spanning the entire temperature range. This model reproduced vital features of channel activation and inactivation. Furthermore, the model also reproduced action potential dependence on temperature. Thus, we provide an essential building block for the generation of biologically detailed models of cortical neurons.


Author(s):  
I. Khidirov ◽  
V. V. Getmanskiy ◽  
A. S. Parpiev ◽  
Sh. A. Makhmudov

This work relates to the field of thermophysical parameters of refractory interstitial alloys. The isochoric heat capacity of cubic titanium carbide TiCx has been calculated within the Debye approximation in the carbon concentration  range x = 0.70–0.97 at room temperature (300 K) and at liquid nitrogen temperature (80 K) through the Debye temperature established on the basis of neutron diffraction analysis data. It has been found out that at room temperature with decrease of carbon concentration the heat capacity significantly increases from 29.40 J/mol·K to 34.20 J/mol·K, and at T = 80 K – from 3.08 J/mol·K to 8.20 J/mol·K. The work analyzes the literature data and gives the results of the evaluation of the high-temperature dependence of the heat capacity СV of the cubic titanium carbide TiC0.97 based on the data of neutron structural analysis. It has been proposed to amend in the Neumann–Kopp formula to describe the high-temperature dependence of the titanium carbide heat capacity. After the amendment, the Neumann–Kopp formula describes the results of well-known experiments on the high-temperature dependence of the heat capacity of the titanium carbide TiCx. The proposed formula takes into account the degree of thermal excitation (a quantized number) that increases in steps with increasing temperature.The results allow us to predict the thermodynamic characteristics of titanium carbide in the temperature range of 300–3000 K and can be useful for materials scientists.


RSC Advances ◽  
2021 ◽  
Vol 11 (41) ◽  
pp. 25731-25737
Author(s):  
Maria Cristina Righetti ◽  
Maria Laura Di Lorenzo ◽  
Patrizia Cinelli ◽  
Massimo Gazzano

At room temperature and at the human body temperature, all the amorphous fraction is mobile in poly(butylene succinate).


Nanophotonics ◽  
2020 ◽  
Vol 9 (14) ◽  
pp. 4233-4252
Author(s):  
Yael Gutiérrez ◽  
Pablo García-Fernández ◽  
Javier Junquera ◽  
April S. Brown ◽  
Fernando Moreno ◽  
...  

AbstractReconfigurable plasmonics is driving an extensive quest for active materials that can support a controllable modulation of their optical properties for dynamically tunable plasmonic structures. Here, polymorphic gallium (Ga) is demonstrated to be a very promising candidate for adaptive plasmonics and reconfigurable photonics applications. The Ga sp-metal is widely known as a liquid metal at room temperature. In addition to the many other compelling attributes of nanostructured Ga, including minimal oxidation and biocompatibility, its six phases have varying degrees of metallic character, providing a wide gamut of electrical conductivity and optical behavior tunability. Here, the dielectric function of the several Ga phases is introduced and correlated with their respective electronic structures. The key conditions for optimal optical modulation and switching for each Ga phase are evaluated. Additionally, we provide a comparison of Ga with other more common phase-change materials, showing better performance of Ga at optical frequencies. Furthermore, we first report, to the best of our knowledge, the optical properties of liquid Ga in the terahertz (THz) range showing its broad plasmonic tunability from ultraviolet to visible-infrared and down to the THz regime. Finally, we provide both computational and experimental evidence of extension of Ga polymorphism to bidimensional two-dimensional (2D) gallenene, paving the way to new bidimensional reconfigurable plasmonic platforms.


Author(s):  
M. P. Silva ◽  
C. G. Rodrigues ◽  
W. A. Varanda ◽  
R. A. Nogueira

1990 ◽  
Vol 201 ◽  
Author(s):  
Honglie Shen ◽  
Genqing Yang ◽  
Zuyao Zhou ◽  
Guanqun Xia ◽  
Shichang Zou

AbstractDual implantations of Si+ and P+ into InP:Fe were performed both at 200°C and room temperature. Si+ ions were implanted by 150keV with doses ranging from 5×1013 /cm2 to 1×1015 /cm2, while P+ ions were implanted by 110keV. 160keV and 180keV with doses ranging from 1×l013 /cm2 to 1×1015 /cm2. Hall measurements and photoluminescence spectra were used to characterize the silicon nitride encapsulated annealed samples. It was found that enhanced activation can be obtained by Si+ and P+ dual implantations. The optimal condition for dual implantations is that the atomic distribution of implanted P overlaps that of implanted si with the same implant dose. For a dose of 5×l014 /cm2, the highest activation for dual implants is 70% while the activation for single implant is 40% after annealing at 750°C for 15 minutes. PL spectrum measurement was carried out at temperatures from 11K to 100K. A broad band at about 1.26eV was found in Si+ implanted samples, of which the intensity increased with increasing of the Si dose and decreased with increasing of the co-implant P+ dose. The temperature dependence of the broad band showed that it is a complex (Vp-Sip) related band. All these results indicate that silicon is an amphoteric species in InP.


2003 ◽  
Vol 13 (12) ◽  
pp. 3827-3834
Author(s):  
ROBERT HINCH

Wolff–Parkinson–White syndrome is a disease where an arrhythmia is caused by the ventricles being electrically excited by an additional accessory pathway that links the atria to the ventricles. The spread of the activation wave from this pathway to the ventricles is modeled using a simplified model of Hodgkin–Huxley sodium channel kinetics, in a two ion-channel model. The model is investigated both analytically (using an asymptotic analysis) and numerically, and both methods are shown to give the same result. It is found that for a given width of the accessory pathway, there is a critical sodium channel density needed for the activation wave to spread from the pathway to the tissue. This result provides an explanation for the success of class-I anti-arrhythmic drugs in treating Wolff–Parkinson–White syndrome.


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