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J Neurophysiol (August 15, 2007). doi:10.1152/jn.00422.2007
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Submitted on April 13, 2007
Accepted on August 10, 2007

Computational model predicts a role for ERG current in repolarizing plateau potentials in dopamine neurons: implications for modulation of neuronal activity

Carmen C. Canavier1*, Sorinel Oprisan2, Joseph Callaway3, Hiufang Ji4, and Paul D. Shepard4

1 Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States; Department of Opthamology, Louisiana State University Health Sciences Center, 2020 Gravier St Suite B, New Orleans, Louisiana, 70112, United States
2 Department of Physics and Astronomy, College of Charleston, Charleston, South Carolina, United States
3 Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, Tennessee, United States
4 Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, Maryland, United States; Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland, United States

* To whom correspondence should be addressed. E-mail: ccanav{at}lsuhsc.edu.

Blocking the small conductance (SK) calcium-activated potassium channel promotes burst firing in dopamine neurons both in vivo and in vitro. In vitro, the bursting is unusual in that spiking persists during the hyperpolarized trough and frequently terminates via depolarization block during the plateau. We focus on the underlying plateau potential oscillation generated in the presence of both apamin and TTX, so that action potentials are not considered. We find that although the plateau potentials are mediated by a voltage-gated Ca2+ current, they do not depend on the accumulation of cytosolic Ca2+ , then utilize a computational model to test the hypothesis that the slowly voltage-activated ether-a-go-go related gene (ERG) potassium current repolarizes the plateaus. The model, which includes a material balance on calcium, is able to reproduce the time course of both membrane potential and somatic calcium concentration, and can also mimic the induction of plateau potentials by the calcium chelator BAPTA. The principle of separation of time scales was used to gain insight into the mechanisms of oscillation and its modulation using nullclines in the phase space. The model predicts that the plateau will be elongated and ultimately result in a persistent depolarization as the ERG current is reduced. This study suggests that the ERG current may play a role in burst termination and the relief of depolarization block in vivo.




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M. Pessia, I. Servettini, R. Panichi, L. Guasti, S. Grassi, A. Arcangeli, E. Wanke, and V. E. Pettorossi
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J. Physiol., October 15, 2008; 586(20): 4877 - 4890.
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