Abstract
An interactive cell modeling web site, iCell (http://ssd1.bme.memphis.edu/icell/), that integrates research and education, was developed to present and to disseminate JAVA-coded models of cellular activities, and to supplement physiology education. iCell can be used to supplement the text-book material as a simulation-based teaching and learning tool. Specifically, iCell allows the students to supplement their learning experiences of the text-book cellular physiology material by running simulations in an interactive environment. The site consists of JAVA-coded models of various cardiac cells and neurons, and provides simulation data of their bioelectric transport activities at cellular level. Each JAVA-coded model allows the user to go through menu options to change model parameters, run and view simulation results. The site also has a glossary section for the scientific terms. iCell has been used as a teaching and learning tool for seven graduate courses at the Joint Biomedical Engineering Program of University of Memphis and University of Tennessee. This modeling tool was also used as a collaboration site among our physiology colleagues interested in simulations of cell membrane activities. Scientists from the fields of biosciences, engineering, life sciences and medical sciences in 17 countries have tested and utilized iCell as a simulation-based teaching, learning and collaboration environment. iCell provides us with an interactive, platform-independent, and user-friendly teaching and learning resource, and also a collaboration environment for electrophysiology to be shared over the Internet. The usage of simulations for teaching and learning will continue advancing simulation-based engineering and sciences for research and development.
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ACKNOWLEDGEMENTS
This publication is based upon independent research/development (IRD) work supported the National Science Foundation (NSF) while Dr. S.S. Demir served at NSF.
The author thanks her students, Joe E. McManis, Yiming Liu, Dong Zhang, Srikanth Padmala and Eswar Damaraju for coding JAVA applets in this project, her student Chris Oehmen and Jing Zheng for posting the html pages and Dr. Emre Velipasaoglu, Siddika Demir and Asim Demir for valuable collaborations and discussions. This research was funded by the Whitaker Foundation (PI, Dr. S. S. Demir).
Any opinion, findings, and conclusions or recommendations expressed in this material are those of the author and do not reflect the views of the National Science Foundation.
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Appendices
APPENDIX: SAMPLE ASSIGNMENT 1
Homework simulation protocols from iCell Version 1b (Neuron Modelbox) assigned to the students taking Life Sciences I for Biomedical Engineers (BIOM 7/8004 at the Joint Biomedical Engineering Program of University of Memphis & University of Tennessee) in 2003.
Please refer to pages 385–398 in your book (Essential Cell Biology by Alberts, Bray, Johnson, Lewis, Raff, Roberts, Walter; Garland Publishing, 1998)1 and specifically review the topics about voltage-gated ion channels, resting membrane potential and Stimulus.
Write a short report of your simulation results.
Hint: Use the cursor to report the changes you observe in voltage (e.g. constant potential level, peak voltage, etc)
Simulation protocols for iCell version 1 (Preview)
Model of a Squid Axon6
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1.
Check the circuit representation for the ionic currents that are present in the model.
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2.
Keep the default values, run the simulations and view the simulations for V and ionic currents for the control conditions.
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3.
Make a table for V peak, V min, and V rest with the control input (stimulus current) for
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Control conditions
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Block I Na by 100% (TTX block)
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Block I K by 100% (TEA block)
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Block I L by 100%
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Determine if you have one or multiple action potentials or none.
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4.
Change I stim from 0 to 200 μA/cm2 in step of 10 μA/cm2 to determine a threshold value for I stim with which a proper action potential is achieved. What is the threshold for I stim to fire a proper action potential?
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5.
Change g Na from 0 to 120 mS/cm2 in step of 10 mS/cm2 to determine a threshold value for g Na with which the neuron fires one action potential. What is the threshold for g Na to fire a proper action potential and what is the percentage of the TTX block?
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6.
Change g Na from 120 to 230 mS/cm2 in step of 10 mS/cm2 to determine a threshold value for g Na with which the system changes from one action potential mode to pacing mode. What is the threshold for g Na to turn the system into an oscillator?
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7.
Prepare a virtual experiment yourself. Write a set of simulation protocols and ask the user to find out certain results.
SAMPLE ASSIGNMENT 2
Homework simulation protocols from iCell Version 1a (Cardiac Modelbox) assigned to the students taking Advanced Cardiac Electrophysiology (BIOM 817 at the Joint Biomedical Engineering Program of University of Memphis & University of Tennessee) in 2000.
Sinoatrial Node Cell Model (Fig. 1)
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1.
Check the circuit representation for the currents that are present in the model.
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2.
Keep the default values, run the simulations and view the simulations for the voltage (V) and ionic currents for the control conditions.
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3.
Block I CaL by 5%, 50% and by 100% (D600 block) and run the simulations for the transient results and steady state results.
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4.
Block I CaT by 100% (Nickel block) and run simulations for the transient results and steady state results.
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5.
Block I f by 100% (Cesium block) and run simulations for the transient results and steady state results.
Rabbit Atrial Cell Model
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1.
Check the circuit representation for the currents that are present in the model.
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2.
Keep the default values, run the simulations and view the simulations for V and ionic currents for the control conditions.
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3.
Block I CaL by 50% and 100% (D600 block) and run the simulations for the transient results and steady state results.
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4.
Block I t by 100% (4AP block) and run the simulations for the transient results and steady state results.
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5.
Stimulate the ventricular cell with a frequency of 1 (Control), 4, 5 and 6 Hz.
Guinea Pig Ventricular Cell Model
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1.
Check the circuit representation for the currents that are present in the model.
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2.
Keep the default values, run the simulations and view the simulations for V and ionic currents for the control conditions.
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3.
Block I Na by 50% and by 100% (TTX block) and run the simulations for the transient results and steady state results.
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4.
Block I K1 by 100% (Barium block) and run simulations for the transient results and steady state results.
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5.
Stimulate the ventricular cell with a frequency of 1 (Control), 2, 3, 4, and 5 Hz.
Human Atrial Cell Model
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1.
Check the circuit representation for the currents that are present in the model.
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2.
Keep the default values, run the simulations and view the simulations for V and ionic currents for the control conditions.
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3.
Block I t by 100% (4AP block) and run the simulations for the transient results and steady state results.
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4.
Block I sus by 100% (TEA block) and run the simulations for the transient results and steady state results.
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5.
Block I Ks by 100% (Propofol block) and run the simulations for the transient results and steady state results.
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6.
Block I Kr by 100% (E4031 block) and run the simulations for the transient results and steady state results.
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Demir, S.S. Interactive Cell Modeling Web-Resource, iCell, as a Simulation-Based Teaching and Learning Tool to Supplement Electrophysiology Education. Ann Biomed Eng 34, 1077–1087 (2006). https://doi.org/10.1007/s10439-006-9138-0
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DOI: https://doi.org/10.1007/s10439-006-9138-0