Details

This Demonstration is an implementation of the mathematical model described in [1] on the effects of impaired cell functioning. The model of the electrical activity of the human cell of Fridlyand et al. [2] was extended by including the relationship between glucose and ATP production showed by Li et al. [3].

In terms of the parameters shown, cell dysfunction is simulated by: (1) inhibiting ATP production; or (2) reducing glucose sensitivity (by increasing the value of the corresponding parameter). This Demonstration considers only the non-oscillatory cases described in the references.

Ionic currents included in the model are:

Type L, T, and P/Q-type Ca2+ current (ICaL, ICaT, ICaP), voltage-gated Na+ current (INa), Na+ background current (INab), delayed rectifier K+ current (IKDr), ERG K+ current (IKhe), ATP-sensitive K+ channel (IKATP), Ca2+ high voltage K+ current (IKCaB), and Ca2+-activated K+ current (IKCa).

The magnitude of the ionic currents depends on the value of the corresponding maximal conductance (gX): gCaL, gCaT, gCaP, gNa, gNaB, gKDr, gKHerg, gKATP, gKCaB, and gKCa.

References

[1] G. J. Félix-Martínez, J. Azpiroz-Leehan, R. Ávila-Pozos, and J. R. Godínez Fernández, “Effects of Impaired ATP Production and Glucose Sensitivity on Human -cell Function: A Simulation Study,” La Revista Mexicana de Ingeniería Biomédica, 35(2), 2014 pp.157–170. www.redalyc.org/pdf/619/61933945006.pdf.

[2] L. E. Fridlyand, D. A. Jacobson, and L. H. Philipson, "Ion Channels and Regulation of Insulin Secretion in Human -cells: a Computational Systems Analysis," Islets, 5(1), 2013 pp. 1–15. doi:10.4161/isl.24166.

[3] J. Li, H. Y. Shuai, E. Gylfe, and A. Tengholm, "Oscillations of Sub-membrane ATP in Glucose-Stimulated Beta Cells Depend on Negative Feedback from Ca2+," Diabetologia, 56(7), 2013 pp. 1577–1586. doi:10.1007/s00125-013-2894-0.