Modeling of action potential generation in NG108-15 cells.
In order to explore the possibility of identifying toxins based on their effect on the shape of action potentials, we created a computer model of the action potential generation in NG108-15 cells (a neuroblastoma/glioma hybrid cell line). To generate the experimental data for model validation, voltage-dependent sodium, potassium, and high-threshold calcium currents, as well as action potentials, were recorded from NG108-15 cells with conventional whole-cell patch-clamp methods. Based on the classic Hodgkin-Huxley formalism and the linear thermodynamic description of the rate constants, ion channel parameters were estimated using an automatic fitting method. Utilizing the established parameters, action potentials were generated using the Hodgkin-Huxley formalism and were fitted to the recorded action potentials. To demonstrate the applicability of the method for toxin detection and discrimination, the effect of tetrodotoxin (a sodium channel blocker) and tefluthrin (a pyrethroid that is a sodium channel opener) was studied. The two toxins affected the shape of the action potentials differently, and their respective effects were identified based on the predicted changes in the fitted parameters.
Molnar
Peter
P
Nanoscience Technology Center, University of Central Florida, Orlando, FL, USA.
Hickman
James J
JJ
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D003521:Cyclopropanes / Q000494:pharmacology; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000502:physiology; D008959:Models, Neurological; D018408:Patch-Clamp Techniques; D013779:Tetrodotoxin / Q000494:pharmacology
D003521:Cyclopropanes; D006845:Hydrocarbons, Fluorinated; D007473:Ion Channels; C489827:2,3,5,6-tetrafluoro-4-methylbenzyl (Z)-(1RS)-cis-3-(2-chloro-3,3,3-trifluoroprop-1-enyl)-2,2-dimethylcyclopropanecarboxylate; D013779:Tetrodotoxin