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.