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


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.


CONCLUSIONS
Transmural heterogeneity of I(Ko) may reduce repolarization gradients in intact myocardium caused by intrinsic ion channel densities, nonuniform strains and electrotonic effects.
Healy
Sarah N
SN
Department of Bioengineering, University of California, San Diego, 92093, USA.
McCulloch
Andrew D
AD
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D003198:Computer Simulation; D006329:Heart Conduction System / Q000502:physiology*; D006352:Heart Ventricles / Q000166:cytology; D007473:Ion Channels / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000502:physiology*; D011817:Rabbits; D013314:Stress, Mechanical; D016276:Ventricular Function
D007473:Ion Channels