© 2005 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved.
An ionic model of stretch-activated and stretch-modulated currents in rabbit ventricular myocytes
Department of Bioengineering and the Whitaker Institute for Biomedical Engineering, University of California San Diego, CA, 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 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.
Key Words: stretch-activated channels, transmural heterogeneity, rabbit cardiomyocyte
*Corresponding author. Department of Bioengineering, 9500 Gilman Drive, Mail Code 0412, La Jolla, CA 92093-0412, USA. Tel.: +1 (858) 534 2547; fax: +1 (858) 534 5722. E-mail address: amcculloch{at}ucsd.edu (A.D. McCulloch).
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