Cell-specific Dynamic Clamp analysis of the role of funny If current in cardiac pacemaking
| Autor: | Annalisa Bucchi, Enrico Ravagli, Stefano Severi, Chiara Bartolucci, Mirko Baruscotti, Dario DiFrancesco, Manuel Paina |
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| Přispěvatelé: | Ravagli, E., Bucchi, A., Bartolucci, C., Paina, M., Baruscotti, M., Difrancesco, D., Severi, S. |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cytological Techniques Biophysics Action Potentials 030204 cardiovascular system & hematology Dynamic Clamp 03 medical and health sciences 0302 clinical medicine Single-cell analysis Heart Rate Isoprenaline Heart rate Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels medicine Animals Ivabradine Funny current Autonomic modulation Molecular Biology Sinoatrial Node Ryanodine receptor Chemistry Sinoatrial node Models Cardiovascular Computational modeling Benzazepines Acetylcholine Electrophysiological Phenomena 030104 developmental biology Clamp medicine.anatomical_structure Cardiac pacemaking Rabbits Single-Cell Analysis medicine.drug |
| Zdroj: | Progress in Biophysics and Molecular Biology. 120:50-66 |
| ISSN: | 0079-6107 |
| DOI: | 10.1016/j.pbiomolbio.2015.12.004 |
| Popis: | We used the Dynamic Clamp technique for i) comparative validation of conflicting computational models of the hyperpolarization-activated funny current, If, and ii) quantification of the role of If in mediating autonomic modulation of heart rate. Experimental protocols based on the injection of a real-time recalculated synthetic If current in sinoatrial rabbit cells were developed. Preliminary results of experiments mimicking the autonomic modulation of If demonstrated the need for a customization procedure to compensate for cellular heterogeneity. For this reason, we used a cell-specific approach, scaling the maximal conductance of the injected current based on the cell's spontaneous firing rate. The pacemaking rate, which was significantly reduced after application of Ivabradine, was restored by the injection of synthetic current based on the Severi-DiFrancesco formulation, while the injection of synthetic current based on the Maltsev-Lakatta formulation did not produce any significant variation. A positive virtual shift of the If activation curve, mimicking the Isoprenaline effects, led to a significant increase in pacemaking rate (+17.3 ± 6.7%, p |
| Databáze: | OpenAIRE |
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