| Dynamical Mechanisms of Pacemaker Generation in IK1-Downregulated Human Ventricular Myocytes: Insights from Bifurcation Analyses of a Mathematical Model Biophysical Journal, Volume 89, Issue 4, 1 October 2005, Pages 2865-2887 Yasutaka Kurata, Ichiro Hisatome, Hiroyuki Matsuda and Toshishige Shibamoto Abstract Dynamical mechanisms of the biological pacemaker (BP) generation in human ventricular myocytes were investigated by bifurcation analyses of a mathematical model. Equilibrium points (EPs), periodic orbits, stability of EPs, and bifurcation points were determined as functions of bifurcation parameters, such as the maximum conductance of inward-rectifier K current (), for constructing bifurcation diagrams. Stable limit cycles (BP activity) abruptly appeared around an unstable EP via a saddle-node bifurcation when was suppressed by 84.6%. After the bifurcation at which a stable EP disappears, the -reduced system has an unstable EP only, which is essentially important for stable pacemaking. To elucidate how individual sarcolemmal currents contribute to EP instability and BP generation, we further explored the bifurcation structures of the system during changes in L-type Ca channel current (), delayed-rectifier K currents (), or Na/Ca exchanger current (). Our results suggest that 1), is, but or is not, responsible for EP instability as a requisite to stable BP generation; 2), is indispensable for robust pacemaking with large amplitude, high upstroke velocity, and stable frequency; and 3), is the dominant pacemaker current but is not necessarily required for the generation of spontaneous oscillations. Abstract | Full Text | PDF (408 kb) |
| Extracting Intramural Wavefront Orientation from Optical Upstroke Shapes in Whole Hearts Biophysical Journal, Volume 95, Issue 2, 15 July 2008, Pages 942-950 Christian W. Zemlin, Olivier Bernus, Arvydas Matiukas, Christopher J. Hyatt and Arkady M. Pertsov Abstract Information about intramural propagation of electrical excitation is crucial to understanding arrhythmia mechanisms in thick ventricular muscle. There is currently a controversy over whether it is possible to extract such information from the shape of the upstroke in optical mapping recordings. We show that even in the complex geometry of a whole guinea pig heart, optical upstroke morphology reveals the 3D wavefront orientation near the surface. To characterize the upstroke morphology, we use , the fractional level at which voltage-sensitive fluorescence, , has maximal time derivative. Low values of indicate a wavefront moving away from the surface, high values of a wavefront moving toward the surface, and intermediate values of a wavefront moving parallel to the surface. We further performed computer simulations using Luo-Rudy II electrophysiology and a simplified 3D geometry. The simulated maps for free wall and apical stimulations as well as for sinus rhythm are in good quantitative agreement with the averaged experimental results. Furthermore, computer simulations show that the effect of the curvature of the heart on wave propagation is negligible. Abstract | Full Text | PDF (1090 kb) |
| Optical Recording System Based on a Fiber Optic Image Conduit: Assessment of Microscopic Activation Patterns in Cardiac Tissue Biophysical Journal, Volume 75, Issue 2, 1 August 1998, Pages 1062-1075 Stephan Rohr and Jan P. Kucera Abstract Optical recording of transmembrane voltage changes with the use of potentiometric dyes has opened the possibility of determining spatial patterns of electrical activity in excitable tissues. To follow such activation patterns on the cellular/subcellular level in heart cell cultures, a recording system was developed that features both high spatial resolution (4–200m) and high temporal resolution (uncertainty in the determination of delays between fast rising signals of ±1s). Central to the system is a fiber optic image conduit consisting of 379 individual optical fibers. At one end the fibers are fused to form an input window that matches the size of the field of view of the microscope. At the other end, the fibers are loose, permitting a selectable subset to be connected to 80 discrete photodetectors. This design allows the sensitive area of the imager to be adapted to regions of interest in a given preparation, thus making optimal use of the limited number of detectors. Furthermore, by using a second fiber optic imager, individual photodetectors can be assigned to different optical ports, thus providing the means for fast and simultaneous dual-emission wavelength measurements. This feature permitted the elimination of motion artifacts arising from the myocytes without the use of contraction-suppressing drugs. Abstract | Full Text | PDF (926 kb) |
Copyright © 1982 The Biophysical Society. All rights reserved.
Biophysical Journal, Volume 40, Issue 3, 255-257, 1 December 1982
doi:10.1016/S0006-3495(82)84481-0
Research Article
B.C. Hill and K.R. Courtney
Muscle contraction can introduce artifact in attempted optical measurements of the action potential in heart tissue stained with voltage-sensitive dyes. Using rabbit sinus node and atrial tissue in vitro, we found that the voltage-sensitive part of the optical signal remains relatively unchanged by variations in the rate of external stimulation or by the application of transmural stimulation (TS), while the contraction-related component can be significantly increased by these same interventions. The relative contributions of membrane voltage and contraction to the optical signal can thus be determined. In particular, the rapid upstroke component of the action potential can be easily identified using this technique.