Mathematical model of the dual action of G protein on the Ca2+ current in identified neurons of the snail Helix aspersa
Correspondencia: Dr. Jesús Pastor Gómez. Servicio de Neurofisiología Clínica. Hospital Ramón y Cajal. Carretera de Colmenar km 9,100. E-28034 Madrid.
E-mail: jesus.pastor@hrc.es
Introduction: The effect of the dopamine on the calcium current of identified cells of the snail Helix aspersa consists on an initial decrease, followed by a subsequent increase when the drug is removed. It had been previously demonstrated that this effect is mediated by a G protein, supposing that the decrease of the current would be mediated by the G alpha subunit, while the increase would be produced by the G beta gamma subunit.
Objective: A mathematical model has been developed with the object to test if the hypothesis of the dual action of the G protein could explain the experimental results.
Material and methods: It has been recording by means of the 'patch-clamp' (whole cell) in identified cells of snail. On the other hand, it has been developed a mathematical model of the calcium current using a Hodgkin-Huxley model, and a simulation of the action of the G protein on this current.
Results: Adjusting the kinetic parameters of the channel by means of the experimental data, it has reproduced in a faithful way the behavior of the calcium current. The simulation of the action of dopamine reproduces the decrease and increase of the current by means of the serial action of the G protein's subunits.
Conclusion: Although a mathematical model cannot demonstrate the logic necessity of the hypotheses on that is based, it is unequivocally demonstrated that the hypothesis is fully compatible with experimental results.
Objetivo Se ha desarrollado un modelo matemático con objeto de comprobar si la hipótesis de la acción dual de la proteína G podría explicar los hallazgos experimentales. Material y métodos. Se registró mediante la técnica de patch-clamp, en configuración de whole cell en células identificadas de caracol. Por otro lado, se desarrolló un modelo matemático de la corriente de calcio utilizando el modelo de Hodgkin y Huxley, y una simulación de la acción de la proteína G sobre dicha corriente.
Resultados Ajustando los parámetros cinéticos del canal por medio de los datos experimentales, se ha reproducido de forma fiel el comportamiento de la corriente de calcio. La simulación de la acción de la dopamina sobre dicha corriente reproduce los efectos de disminución y aumento de la corriente debidos a la acción consecutiva de las subunidades de la proteína G.
Conclusiones A pesar de que un modelo matemático no puede demostrar la necesidad lógica de las hipótesis en que se basa, sí se demuestra inequívocamente que la hipótesis es plenamente compatible con los resultados