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 sim ilar to the CA1 hippocampal neuron sodium channel model developed by Kuo an d Bean (1994. Neuron. 12:819-829) with the following modifications: 1) an a dditional open state is added; 2) open-inactivated transitions are made vol tage-dependent; and 3) channel rate constants are exponential function of e nthalpy, entropy, and voltage and have explicit temperature dependence. Mod el parameters are determined using a simulated annealing algorithm to minim ize the error between model responses and various experimental data sets.:T he model reproduces a wide range of experimental data including ionic curre nts, gating currents, tail currents, steady-state inactivation, recovery fr om inactivation, and open time distributions over a temperature range of 10 degrees C to 25 degrees C. The model also predicts measures of single chan nel activity such as first latency, probability of a null sweep, and probab ility of reopening.