Diffusion–convection effects on drug distribution at the cell membrane level in a patch-clamp setup
| Autor: | Adrian Iftime, Anca Alexandra Popescu, Irina Baran |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Statistics and Probability
Agonist Convection Patch-Clamp Techniques Time Factors Materials science medicine.drug_class Vasodilator Agents Diffusion Models Biological Signal General Biochemistry Genetics and Molecular Biology Membrane Potentials Cell membrane Cell Line Tumor medicine Humans Patch clamp Simulation Applied Mathematics Cell Membrane Pipette Biological Transport General Medicine Acetylcholine Amplitude medicine.anatomical_structure Modeling and Simulation Biophysics Algorithms |
| Zdroj: | Biosystems. 102:134-147 |
| ISSN: | 0303-2647 |
| DOI: | 10.1016/j.biosystems.2010.09.003 |
| Popis: | We present a model-based method for estimating the effective concentration of the active drug applied by a pressure pulse to an individual cell in a patch-clamp setup, which could be of practical use in the analysis of ligand-induced whole-cell currents recorded in patch-clamp experiments. Our modelling results outline several important factors which may be involved in the high variability of the electric response of the cells, and indicate that with a pressure pulse duration of 1 s and diameter of the perfusion tip of 600 μm, elevated amounts of drug can accumulate locally between the pipette tip and the cell. Hence, the effective agonist concentration at the cell membrane level can be consistently higher than the initial concentration inside the perfusion tubes. We performed finite-difference and finite-element simulations to investigate the diffusion/convection effects on the agonist distribution on the cell membrane. Our model can explain the delay between the commencement of acetylcholine application and the onset of the whole-cell current that we recorded on human rhabdomyosarcoma TE671 cells, and reproduce quantitatively the decrease of signal latency with the concentration of agonist in the pipette. Results also show that not only the geometry of the bath chamber and pipette tip, but also the transport parameters of the diffusive and convective phenomena in the bath solution are determinant for the amplitude and kinetics of the recorded currents and have to be accounted for when analyzing patch-clamp data. |
| Databáze: | OpenAIRE |
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