Multiscale Determinants of Delayed Afterdepolarization Amplitude in Cardiac Tissue
| Autor: | Michael B. Liu, Zhilin Qu, James N. Weiss, Christopher Y. Ko, Zhen Song |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Patch-Clamp Techniques Intracellular Space Biophysics chemistry.chemical_element Arrhythmias Biology Calcium Cardiovascular Membrane Potentials Afterdepolarization 03 medical and health sciences Models Caffeine Extracellular Animals Myocyte Myocytes Cardiac Computer Simulation Calcium Signaling Patch clamp Fluorescent Dyes Calcium signaling Membrane potential Systems Biophysics Myocytes Aniline Compounds Models Cardiovascular Arrhythmias Cardiac Cardiovascular Agents Anatomy Biological Sciences Voltage-Sensitive Dye Imaging Sarcoplasmic Reticulum 030104 developmental biology Xanthenes chemistry Physical Sciences Chemical Sciences Cardiovascular agent Rabbits Cardiac |
| Zdroj: | Biophysical journal, vol 112, iss 9 Ko, CY; Liu, MB; Song, Z; Qu, Z; & Weiss, JN. (2017). Multiscale Determinants of Delayed Afterdepolarization Amplitude in Cardiac Tissue. BIOPHYSICAL JOURNAL, 112(9), 1949-1961. doi: 10.1016/j.bpj.2017.03.006. UCLA: Retrieved from: http://www.escholarship.org/uc/item/0h13157g |
| ISSN: | 0006-3495 |
| DOI: | 10.1016/j.bpj.2017.03.006 |
| Popis: | Spontaneous calcium (Ca) waves in cardiac myocytes underlie delayed afterdepolarizations (DADs) that trigger cardiac arrhythmias. How these subcellular/cellular events overcome source-sink factors in cardiac tissue to generate DADs of sufficient amplitude to trigger action potentials is not fully understood. Here, we evaluate quantitatively how factors at the subcellular scale (number of Ca wave initiation sites), cellular scale (sarcoplasmic reticulum (SR) Ca load), and tissue scale (synchrony of Ca release in populations of myocytes) determine DAD features in cardiac tissue using a combined experimental and computational modeling approach. Isolated patch-clamped rabbit ventricular myocytes loaded with Fluo-4 to image intracellular Ca were rapidly paced during exposure to elevated extracellular Ca (2.7 mmol/L) and isoproterenol (0.25 μmol/L) to induce diastolic Ca waves and subthreshold DADs. As the number of paced beats increased from 1 to 5, SR Ca content (assessed with caffeine pulses) increased, the number of Ca wave initiation sites increased, integrated Ca transients and DADs became larger and shorter in duration, and the latency period to the onset of Ca waves shortened with reduced variance. In silico analysis using a computer model of ventricular tissue incorporating these experimental measurements revealed that whereas all of these factors promoted larger DADs with higher probability of generating triggered activity, the latency period variance and SR Ca load had the greatest influences. Therefore, incorporating quantitative experimental data into tissue level simulations reveals that increased intracellular Ca promotes DAD-mediated triggered activity in tissue predominantly by increasing both the synchrony (decreasing latency variance) of Ca waves in nearby myocytes and SR Ca load, whereas the number of Ca wave initiation sites per myocyte is less important. |
| Databáze: | OpenAIRE |
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