Numerical studies of use-dependent block of cardiac sodium channels by quinidine on spiral wave reentry

Abstract

A numerical model of quinidine induced use-dependent blockade of cardiac sodium channels based on the modulated receptor hypothesis of Hille (1977) and Hondeghem and Katzung (1977) was developed. Model rate constants for transitions between non-drug bound and drug bound states were determined by fitting model responses to experimental data. The drug block model was incorporated into the Oxsoft HEART V4.2 single ventricular cell model, which in turn was used to construct two-dimensional ventricular cell networks. Spiral wave reentry was initiated in the two-dimensional networks and a step increase in quinidine concentration was applied uniformly to each cell. Core position was fixed in the absence of drug. In the presence of drug, core position underwent large spatial translations. As a result of these translations, individual cells exhibited action potentials with highly variable amplitude and interbeat interval.