Temperature-dependent model of human cardiac sodium channel
Authors
Abstract:
Cardiac sodium channels are integral membrane proteins whose structure is not known at atomic level yet and their molecular kinetics is still being studied through mathematical modeling. This study has focused on adapting an existing model of cardiac Na channel to analyze molecular kinetics of channels at 9-37°C. Irvine et al developed a Markov model for Na channel using Neuronal Network Model as a framework. They produced state diagram for channel with 5 close, 2 open, and 5 close-inactivated and one inactivated states. Transitions are expressed as ?H and ?S and an effective valence (z) terms. Almost all of rate constants are voltage and temperature dependent. The model fails to reproduce kinetics at temperature higher than 25°C. A practical approach would be to scale up each rate constant by its own Q10. As temperature is increased, time constants and recovery rate decrease and increase respectively. First latencies decrease with temperature at (–100)-20 mV. Open probability of channels does not follow temperature suggesting that at higher temperature a larger fraction of channels are inactivated before they reach open state. This study exhibits a reasonable model for single channel ionic current and its recovery from inactivation for a voltage range of (–100)-20 mV at 9-37°C. Our approach may lead to more detailed molecular kinetics of Na channels resulting in better understanding of arrhythmias and Na channel based nervous system malfunction.
similar resources
Cardiac sodium channel Markov model with temperature dependence and recovery from inactivation.
A Markov model of the cardiac sodium channel is presented. The model is similar to the CA1 hippocampal neuron sodium channel model developed by Kuo and Bean (1994. Neuron. 12:819-829) with the following modifications: 1) an additional open state is added; 2) open-inactivated transitions are made voltage-dependent; and 3) channel rate constants are exponential functions of enthalpy, entropy, and...
full textUse-Dependent Block of Human Cardiac Sodium Channels by GS967.
GS-458967, 6-(4-(Trifluoromethoxy)phenyl)-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine (GS967) is a recently described, novel, sodium channel inhibitor exhibiting potent antiarrhythmic effects in various in vitro and in vivo models. The antiarrhythmic mechanism has been attributed to preferential suppression of late sodium current. However, there has been no reported systematic investigat...
full textBiology of cardiac sodium channel Nav1.5 expression.
Na(v)1.5, the pore forming α-subunit of the voltage-dependent cardiac Na(+) channel, is an integral membrane protein involved in the initiation and conduction of action potentials. Mutations in the gene-encoding Na(v)1.5, SCN5A, have been associated with a variety of arrhythmic disorders, including long QT, Brugada, and sick sinus syndromes as well as progressive cardiac conduction defect and a...
full textCardiac sodium channel regulator MOG1 regulates cardiac morphogenesis and rhythm
MOG1 was initially identified as a protein that interacts with the small GTPase Ran involved in transport of macromolecules into and out of the nucleus. In addition, we have established that MOG1 interacts with the cardiac sodium channel Nav1.5 and regulates cell surface trafficking of Nav1.5. Here we used zebrafish as a model system to study the in vivo physiological role of MOG1. Knockdown of...
full textMy Resources
Journal title
volume Volume 3 issue Supplement 1
pages 118- 118
publication date 2010-11-20
By following a journal you will be notified via email when a new issue of this journal is published.
Hosted on Doprax cloud platform doprax.com
copyright © 2015-2023