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An ionic model of stretch-activated and stretch-modulated currents in rabbit ventricular myocytes
Sarah N Healy1, Andrew D McCulloch
1Department of Bioengineering, University of California, San Diego, 92093, USA.
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 I(ns), 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 (APD(20)) and action potential amplitude, an elevated resting transmembrane potential and either an increase or decrease in APD(90), depending on the reversal potential of I(ns). A stretch-induced decrease in I(K1) (70%), plus a small I(ns) current (g(ns) = 10 pS), results in a reduction in APD(20) and increase in APD(90), and a reduced safety factor for conduction. Increasing I(K1) (150%) plus a large I(ns) current (g(ns) = 40 pS), also leads to a reduction in APD(20) and increase in APD(90), 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) I(Ko) results in action potential shortening.
Conclusion:
Transmural heterogeneity of I(Ko) may reduce repolarization gradients in intact myocardium caused by intrinsic ion channel densities, nonuniform strains and electrotonic effects.
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