An ionic model of stretch-activated and stretch-modulated currents in rabbit ventricular myocytes

Abstract

Abstract Aims To develop an ionic model of stretch-activated and stretch-modulated currents in rabbit ventricular myocytes consistent with experimental observations, that can be used to investigate the role of these currents in intact myocardium. Methods and results A non-specific cation-selective stretch-activated current Ins, was incorporated into the Puglisi–Bers ionic model of epicardial, endocardial and midmyocardial ventricular myocytes. Using the model, we predict a reduction in action potential duration at 20% repolarization (APD20) and action potential amplitude, an elevated resting transmembrane potential and either an increase or decrease in APD90, depending on the reversal potential of Ins. A stretch-induced decrease in IK1 (70%), plus a small Ins current (gns=10 pS), results in a reduction in APD20 and increase in APD90, and a reduced safety factor for conduction. Increasing IK1 (150%) plus a large Ins current (gns=40 pS), also leads to a reduction in APD20 and increase in APD90, but with a greater safety factor. Endocardial and midmyocardial cells appear to be the most sensitive to stretch-induced changes in action potential. The addition of the K+-specific stretch-activated current (SAC) IKo results in action potential shortening. Conclusion Transmural heterogeneity of IKo may reduce repolarization gradients in intact myocardium caused by intrinsic ion channel densities, nonuniform strains and electrotonic effects.