Paradoxical Loss of Excitation with High Intensity Pulses During Electric Field Stimulation of Single Cardiac Cells
Vinod Sharma 1, Robert Susil 1 and Leslie Tung 1*
1 The Johns Hopkins University
* To whom correspondence should be addressed. E-mail: ltung{at}bme.jhu.edu.
Submitted on June 22, 2004
Revised on July 14, 2004
Accepted on 23 November 2004
 |
Abstract |
|---|
Transmembrane potential responses of single cardiac cells stimulated at rest were studied with uniform rectangular field pulses having durations of 0.5 to 10 ms. Cells were enzymatically isolated from guinea pig ventricles, stained with voltage sensitive dye di-8-ANEPPS, and stimulated along their long axes. Fluorescence signals were recorded with spatial resolution of 17 µm from up to 11 sites along the cell. With 5 and 10 ms pulses all cells (n=10) fired an action potential over a broad range of field amplitudes (~3 to 65 V/cm). With 0.5 and 1 ms pulses all cells (n=7) fired an action potential for field amplitudes ranging from the threshold value (~4-8 V/cm) to 50-60 V/cm. However, when the field amplitude was further increased, 5 of 7 cells failed to fire an action potential. We postulated that this paradoxical loss excitability for higher amplitude field pulses is the result of nonuniform polarization of the cell membrane under conditions of electric field stimulation, and a counterbalancing interplay between sodium current (INa) and inwardly rectifying potassium current (IK1) with increasing field strength. This hypothesis was verified using computer simulations of a field-stimulated guinea pig ventricular cell. In conclusion, we show that for stimulation with short duration pulses, cells can be excited for fields ranging between a low amplitude excitation threshold (lower limit of excitation: LLE) and a high amplitude threshold (upper limit of excitation: ULE) above which the excitation is suppressed. These results can have implications for the mechanistic understanding of defibrillation outcome, especially in the setting of diseased myocardium.
Key Words:
cellular electrophysiology, membrane potential, optical monitoring
