Effects of Elevated Extracellular Potassium on the Stimulation Mechanism of Diastolic Cardiac Tissue  Veniamin Y. Sidorov, Marcella C. Woods, John P. Wikswo  Biophysical Journal  Volume 84, Issue 5, Pages 3470-3479 (May 2003) DOI: 10.1016/S0006-3495(03)70067-8 Copyright © 2003 The Biophysical Society Terms and Conditions

FIGURE 1 Anodal-make response to diastolic 3× threshold stimulation for normal [K+]o (4mM). The anodal S2 stimulus was 6mA in amplitude, 10ms in duration, and applied at an S1-S2 coupling interval of 350ms. (A) Image of the transmembrane potential distribution 2ms after the onset of S2 point stimulation at the center of the image. (B) Four representative traces recorded within the virtual cathode (red) and virtual anode (blue) areas. The pixel locations for these traces are marked with white and black dots in A. (C and D) Time-space plots for lines longitudinal and transverse to the fiber direction (white and black dashed lines in A). The white horizontal isochronal line corresponds to 8ms after the beginning of S2. The white slanted lines in C demonstrate the inward and outward propagation velocity along the fiber direction. The white slanted lines in D demonstrate the outward propagation velocity transverse to the fiber direction. The blue and red arrows indicate the location of the pixels depicted by black and white dots in A. (E) The transmembrane potential distribution as a function of time. The numbers in the upper right represent the time [ms] since the onset of S2. Biophysical Journal 2003 84, 3470-3479DOI: (10.1016/S0006-3495(03)70067-8) Copyright © 2003 The Biophysical Society Terms and Conditions

FIGURE 2 Anodal-make response to diastolic threshold stimulation for normal [K+]o (4mM). The anodal S2 stimulus was 2mA in amplitude, 10ms in duration, and applied at an S1-S2 coupling interval of 350ms. (A) Image of the transmembrane potential distribution 10ms after the onset of S2 point stimulation at the center of the image. (B) Four representative traces recorded within the virtual cathode (red) and virtual anode (blue) areas. The pixel locations for these traces are marked with white and black dots in A. (C and D) Time-space plots for lines longitudinal and transverse to the fiber direction (white and black dashed lines in A). The white horizontal isochronal line corresponds to 16ms after the beginning of S2. The white slanted lines demonstrate propagation velocity along (C) and transverse (D) to the fiber direction. The blue and red arrows indicate the location of the pixels depicted by black and white dots in A. (E) The transmembrane potential distribution as a function of time. The numbers in the upper right represent the time [ms] since the onset of S2. Biophysical Journal 2003 84, 3470-3479DOI: (10.1016/S0006-3495(03)70067-8) Copyright © 2003 The Biophysical Society Terms and Conditions

FIGURE 3 Anodal-break response to strong systolic stimulation for normal [K+]o (4mM). The anodal S2 stimulus was 20mA in amplitude, 150ms in duration, and applied at an S1-S2 coupling interval of 80ms. (A) Representative traces recorded within the virtual cathode (red) and virtual anode (blue) area depicting the response to S1 and S2 stimulation. The black arrows underneath the plot show the stimulus timing. (B) Image of the transmembrane potential distribution 82ms after the onset of S2 point stimulation at the center of the image. The pixel locations for the traces in A and C are indicated by the white and black dots. (C) Four representative traces recorded within the virtual cathode (red) and virtual anode (blue) areas depicting the response at the end of S2 and after S2 termination. (D and E) Time-space plots for lines longitudinal and transverse to the fiber direction (white and black dashed lines in B). The white horizontal isochronal line corresponds to the termination of S2. The white slanted lines demonstrate propagation velocity along (D) and transverse (E) to the fiber direction. The blue and red arrows indicate the location of the pixels depicted by black and white dots in B. Data artifacts caused by the testing electrode lie underneath the black W's in the images of B and D. (F) The transmembrane potential distribution as a function of time. The numbers in the upper right represent the time [ms] since the termination of S2. Biophysical Journal 2003 84, 3470-3479DOI: (10.1016/S0006-3495(03)70067-8) Copyright © 2003 The Biophysical Society Terms and Conditions

FIGURE 4 Anodal-break response to diastolic threshold stimulation for elevated [K+]o (8mM). The anodal S2 stimulus was 6mA in amplitude, 10ms in duration, and applied at an S1-S2 coupling interval of 350ms. (A) Image of the transmembrane potential distribution 8ms after the onset of S2 point stimulation at the center of the image. (B) Four representative traces recorded within the virtual cathode (red) and virtual anode (blue) areas. The pixel locations for these traces are marked with white and black dots in A. (C and D) Time-space plots for lines longitudinal and transverse to the fiber direction (white and black dashed lines in A). The white horizontal isochronal line corresponds to the termination of S2. The white slanted lines demonstrate propagation velocity along (C) and transverse (D) to the fiber direction. The blue and red arrows indicate the location of the pixels depicted by black and white dots in A. (E) The transmembrane potential distribution as a function of time. The numbers in the upper right represent the time [ms] since the onset of S2. Biophysical Journal 2003 84, 3470-3479DOI: (10.1016/S0006-3495(03)70067-8) Copyright © 2003 The Biophysical Society Terms and Conditions

FIGURE 5 Wave front and virtual cathode location for normal (4mM) and elevated (8mM) [K+]o. Images of the transmembrane potential distribution for (A) elevated and (B) normal [K+]o. The smaller ellipses depict the virtual cathode locations, and the large ellipses describe the propagating wave fronts. (C and D) The time-space plots constructed along the (C) green and (D) blue lines in A. The white horizontal isochronal line corresponds to the termination of S2. The white slanted lines show propagation velocity along the axes in A. Biophysical Journal 2003 84, 3470-3479DOI: (10.1016/S0006-3495(03)70067-8) Copyright © 2003 The Biophysical Society Terms and Conditions

FIGURE 6 Microelectrode measurements of transmembrane potential for normal (4mM) and elevated (8mM) [K+]o. Typical action potentials recorded using microelectrodes for (A) normal and (B) elevated [K+]o. Biophysical Journal 2003 84, 3470-3479DOI: (10.1016/S0006-3495(03)70067-8) Copyright © 2003 The Biophysical Society Terms and Conditions