Abstract Details
| Presented By: | McNary, Thomas |
| Affiliated with: | University of Utah, Biomedical Engineering |
| Authors: | Thomas G. McNary, Kenneth W. Spitzer, Frank B. Sachse |
| From: | Biomedical Engineering Department, Physiology Department, Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah |
Title
Abstract
Mechanisms underlying the relationship between mechanical strain and electrical conduction velocity (Θ) in cardiac muscle are incompletely understood. In this study we examined the effect of strain on the passive electrical properties of isolated ventricular myocytes, namely membrane conductance (Gm) and membrane capacitance (Cm). These parameters were varied in our model to simulate the effects of strain. Due to GK1 being the predominant ion channel conductance at rest, Gm was modeled as GK1.
The experiments were performed on resting rabbit ventricular myocytes held in a glass-bottom, flow-through cell chamber at 35ºC. Glass micro-pipettes with tips bent at 60º angles and coated with laminin were attached to each end of a cell in order to apply approximately 10% strain. Cells were voltage clamped (ruptured patch) via a suction pipette positioned near the center of the cell. Before and during application of strain Cm and Gm were measured by applying 5mV hyperpolarizing steps with a duration of 200 ms from a holding potential of -80mV.
We modeled the effects of Gk1 and Cm on Θ and the maximum upstroke velocity of the action potential (dVm/dt) in a one dimensional tissue strand. Myocytes in the strand were represented by an electrophysiology model for the guinea-pig ventricular myocyte (Noble et al., 1998). Gk1 was systematically varied ±30% from the control value of 0.5µS, while Cm was varied by +20 and -30% of 95pF.
Measurements of Cm and Gm at 0% strain were 139±17pF (mean±SE, n=7) and 12±2.1MΩ respectively. Analysis of our preliminary measured data showed that strain decreased Gm by 20.2±6.7%. The response of Cm to straining was more variable decreasing by 4.4±9.0%. Simulation data showed a decrease in Θ of 12% at 120% Cm and a 30% increase in Θ at 70% Cm. dVm/dt was reduced (-9%) at 120% Cm, while 70% Cm caused dVm/dt to increase by 19%. The change in Θ due to varied Gk1 was less pronounced. Increasing Gk1 by 30% reduced Θ to 45.7 cm/s (-3%) and decreasing Gk1 by 30% increased Θ to 48.9 cm/s (+3%). Resting Vm and dVm/dt remained virtually unchanged (<1%) as Gk1 was varied.
Our measurements indicate that both Gm and Cm change under mechanical strain. The simulation data suggest an important role of Cm in strain-Θ relationships. Detailed measurement of strain-modulated Cm appears necessary to understand strain-modulation of Θ.