The roles of stretch-activated channels on antiarrhythmic therapies: computer simulations

The recognition of abnormal ventricular stretch as a potent arrhythmogenic factor that can be modulated by chemical agents has opened new avenues for anti-arrhythmia therapy. Experimental evidences showed that the depolarized currents induced by stretch-activated channels (SACs) could lead to arrhythmias. The major objective of this study is to explore the interactions between SACs and gap junctions on modulating the action potential. A of rat ventricular cell model is developed based on the dynamical equations described by Beeler and Reuter (1977). Two cells are connected together by gap junctions, which are modeled as a T-network of resistances. While an external current stimulus is applied on the first cell, the action potential is measured at the second cell in the stretch status based on a Poisson ratio of 0.7. Results indicate that (1) under the status of cell uncoupling, the measured maximum amplitude of action potential is reduced from 25 mV to -10 mV, the action potential duration is shortened from 300 ms to 150 ms, and the membrane potential is elevated from -82 mV to -60 mV; (2) under the condition of cell coupling, the measured overshoot amplitude of action potential is reduced slightly from 25 mV to 22 mV, the action potential duration is lengthened slightly from 300 ms to 320 ms with the crossover near -40 mV, and the membrane potential is elevated to -70 mV. In conclusions, the presence of SACs in cellular uncoupling can be arrhythmogenic. The targets for therapies are likely to be the interactions between SACs and gap junctions