Rectification of the Background Potassium Current

Abstract

Abstract-Ventricular fibrillation (VF) is the leading cause of sudden cardiac death. Yet, the mechanisms of VF remain elusive. Pixel-by-pixel spectral analysis of optical signals was carried out in video imaging experiments using a potentiometric dye in the Langendorff-perfused guinea pig heart. Dominant frequencies (peak with maximal power) were distributed throughout the ventricles in clearly demarcated domains. The fastest domain (25 to 32 Hz) was always on the anterior left ventricular (LV) wall and was shown to result from persistent rotor activity. Intermittent block and breakage of wavefronts at specific locations in the periphery of such rotors were responsible for the domain organization. Patch-clamping of ventricular myocytes from the LV and the right ventricle (RV) demonstrated an LV-to-RV drop in the amplitude of the outward component of the background rectifier current (I B ). Computer simulations suggested that rotor stability in LV resulted from relatively small rectification of I B (presumably I K1 ), whereas instability, termination, and wavebreaks in RV were a consequence of strong rectification. This study provides new evidence in the isolated guinea pig heart that a persistent high-frequency rotor in the LV maintains VF, and that spatially distributed gradients in I K1 density represent a robust ionic mechanism for rotor stabilization and wavefront fragmentation.

Universal scaling law of electrical turbulence in the mammalian heart

“…Some areas excite at higher rates than others and the DFs organize in clearly demarcated domains. As demonstrated in hearts from guinea pigs and mice (4,13), the frequency of the vortices, or their rotation period (1/frequency), closely matched the frequency of fibrillation or cycle length calculated from the DF maps or the ECG. However, please note that the highest DF domain decreases with increasing body size (mouse, 38 Hz; guinea pig, 26 Hz; rabbit, 15 Hz; human, 6.8 Hz).…”

“…One school of thought suggests that, during fibrillation, the electrical waves propagate through the ventricles at random, with no underlying deterministic organization (2,3). Others postulate that, although VF is complex, it is maintained by organized electrical vortices, called ''rotors,'' that spin at exceedingly high frequencies around a central core region (4). Waves shed by the rotors take a spiral shape near the core but may turn into disorganized patterns of propagation known as ''fibrillatory conduction'' in the rotor's periphery (4).…”

“…Others postulate that, although VF is complex, it is maintained by organized electrical vortices, called ''rotors,'' that spin at exceedingly high frequencies around a central core region (4). Waves shed by the rotors take a spiral shape near the core but may turn into disorganized patterns of propagation known as ''fibrillatory conduction'' in the rotor's periphery (4). Based on normal electrophysiology and anatomy, it is suggested that all mammalian hearts are built on the same template (5), and fibrillation has been shown to occur in the hearts of all mammalian species studied to date, from the mouse to the horse.…”

Negative filament tension in the Luo-Rudy model of cardiac tissue

“…by one stable high frequency source mother rotor and complex VF patterns are the result of multiple breaks of the waves from this source at heterogeneities of the heart [3]. The multiple wavelet hypothesis explains VF by breakup of spiral waves due to dynamical or anatomical heterogeneity [4,5].…”

Arrhythmogenesis in the heart: Multiscale modeling of the effects of defibrillation shocks and the role of electrophysiological heterogeneity

“…13 The reasons for the modification of the ionic model from its original version are the following. A singlecell electrophysiological study by Samie et al 14 have shown that LV myocardial cells have larger background potassium current as compared to RV cells. The study by Samie et al incorporated spline functions in the LR1 model (available at the journal website) to represent the experimental current-voltage relationship the authors obtained for isolated LV and RV cells.…”