Session S74.2

Modeling Effects of Strain-Modulated Membrane Capacitance and Conductance of K+ Inward-Rectifier on Conduction Velocity in Cardiac Tissue

TG McNary*, FB Sachse

University of Utah
Salt Lake City, UT, USA

Controversy exists concerning the effects of mechanical strain on electrical conduction velocity (T) in cardiac tissue. Increasing strain has been associated with a decrease, a biphasic response, and an increase in T. In this study we focused on electrical membrane properties at rest, in particular the conductance of the inward rectifying K+ channel (Gk1) and the membrane capacitance (Cm), and how their modulation by strain can affect T. Gk1 is the major contributor to membrane conductance of myocytes at rest and several studies suggested that straining decreases Gk1. Other studies suggested that straining increases Cm. Electron-microscopic images demonstrated unfolding of membrane invaginations with strain, which may explain increased Cm with strain.
This study explores the possible effects of strain-modulated GK1 and Cm on T using a computational approach. Electrical conduction was simulated by a mono-domain model of a one dimensional tissue strand. The strand had a length of 2.4 mm and was discretized every 0.1 mm. Myocytes were represented by the Noble et al. model of electrophysiology of guinea-pig ventricular cells. The coupling resistance was 1.25 MO. The ordinary differential equations underlying the arrangements were solved using the Euler method with a time step of 1 µs. To explore strain modulation we varied the original Cm of 95 µF in the range of -20 to +20% and the original Gk1 of 0.5 µS in the range of -30 to +20%. Simulation results were analyzed after the 10th stimulation. The analysis yielded T, upstroke velocity of the transmembrane voltage, and resting membrane voltage.
The analysis showed an approximately linear decrease in T with increase in Cm. For instance, T decreased to 41.1 cm/s with +20% in Cm and increased to 55.6 cm/s with –20% where the T was originally 47.2 cm/s. Upstroke velocity was barely influenced (<1%) by a 20% increase in capacitance. On the other hand, when Cm was decreased by 20% the upstroke velocity increased by 11%. The change in T due to varied Gk1 was less pronounced. A change of +20% and -30% of Gk1 caused decreasing of T to 46.2 cm/s and increasing to 48.9 cm/s, respectively. The upstroke velocity and resting membrane potentials remained virtually unchanged (<1%) as Gk1 was varied.
Our study indicates that establishing the cellular relationship between strain and GK1 as well as strain and Cm will be necessary to understand measured strain-T relationships in tissue. Significant modulation of GK1 appears required to affect T. In contrast, relatively small changes of Cm have a strong effect on T. We suggest that these results are highly relevant for dissection of the various biophysical mechanisms that underlie measured strain-T relationships.

(Abstract Control Number: 102)