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This article is part of the supplement: Nineteenth Annual Computational Neuroscience Meeting: CNS*2010

Open Access Poster Presentation

Role of low and high-voltage activated Ca2+-dependent K+ currents in the control of alpha-motoneuron discharge and its implication in hyperreflexia

Sharmila Venugopal1, Thomas M Hamm13 and Ranu Jung12*

Author Affiliations

1 Center for Adaptive Neural Systems, Arizona State University, Tempe, AZ-85287, USA

2 School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ-85287, USA

3 Barrow Neurological Institute, Phoenix, AZ-85013, USA

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BMC Neuroscience 2010, 11(Suppl 1):P158  doi:10.1186/1471-2202-11-S1-P158

The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-2202/11/S1/P158


Published:20 July 2010

© 2010 Jung et al; licensee BioMed Central Ltd.

Poster Presentation

Specificity of calcium-activated potassium (K+) currents to different sources of calcium has been noted in many neurons (e.g.1). Recently, in spinal alpha-motoneurons (α-MN), it was shown that the low-voltage activated L-type calcium currents (also known as persistent calcium currents) activate an exclusive subset of small conductance K+ currents (SKL)2. The SKL currents were distinct from the medium after-hyperpolarization (mAHP) producing N/P-type calcium activated K+ currents (SKAHP currents). The same study further suggested that an enhancement of persistent calcium current often observed after chronic spinalization can in part be due to reduced availability of the SKL channels albeit mAHP remained unchanged. While mAHP has been suggested to be integral in controlling motoneuron firing frequencies and grading L-Ca activation, the role of SKL currents in motoneuron discharge is unknown. The goal of this study is to characterize the influence of SKAHP and SKL currents on motoneuron firing frequencies. Here we test the hypothesis that SKAHP and SKL currents play differential roles in the control of persistent inward currents that are key determinants of motoneuron excitability.

Methods

The α-MN is modeled with two compartments (soma and dendrite) using conductance-based Hodgkin-Huxley formalism. The persistent L-Ca and SKL are located in the dendrite along with persistent sodium current. The mAHP causing high-voltage activated Ca2+ and SKAHP currents are confined to the soma along with action potential causing fast sodium and delayed rectifier K+ currents. Model simulations are performed using the XPPAUT software.

Results

The model α-MN shows counter-clockwise hysteresis in the injected current-frequency (I-f) relationship (Fig. 1, control) as observed in many chronic spinal sacrocaudal motoneurons. This hysteresis is mediated by the dendritic L-Ca and persistent sodium currents (together termed PIC). A selective blockade of somatic SKAHP greatly increases the spike frequencies consistent with experimental findings that mAHP is integral for controlling α-MN frequencies. On the other hand, eliminating SKL resulted in uncontrolled L-Ca activation with virtually no deactivation of the persistent inward currents even with large hyperpolarization (self-sustained discharge for ISOMA ≤ 0 does not terminate; compare with SKAHP = 0 and control traces).

Conclusions

Chronic spinal cord injury often results in spasticity (hyperreflexia). Intrinsic hyper excitability of α-MN has been attributed to underlie hyperreflexia. The uncontrolled and abrupt PIC activation due to reduction in SKL currents implicates rapid development and sustenance of muscle contraction forces such as during spasms, thus delineating a possible mechanism for α-MN hyper excitability that could lead to hyperreflexia following injury.

thumbnailFigure 1. I-f curves; Bounded by green ovals are frequencies during PIC development; pink circles denote PIC termination

Acknowledgements

This work was supported by NIH R01-NS054282.

References

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    Nature 1998, 395:900-905. PubMed Abstract | Publisher Full Text OpenURL

  2. Li X, Bennett DJ: Apamin-sensitive calcium-activated potassium currents (SK) are activated by persistent calcium currents in rat motoneurons.

    J Neurophysiol 2007, 97:3314-3330. PubMed Abstract | Publisher Full Text OpenURL