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KIR current inactivation modulates dendritic calcium in medium spiny neurons

Background

The membrane potential of striatal medium spiny neurons (MSNs) fluctuates between down- and up-states. In ventral striatum, inward rectifying potassium (KIR) currents in 40% of MSNs inactivate [1]. KIR current inactivation appears to alter spike frequency and onset during up-states [2]. However, it is not known whether these translate into significant changes in calcium dynamics in the dendrites. We describe a computational study investigating how this inactivation influences dendritic calcium transients.

Methods

Two MSNs were modeled using NEURON, one equipped with non-inactivating KIR currents (henceforth, "non-inKIR") and the other with inactivating KIR currents (henceforth "inKIR") and their dendritic calcium transients were compared in response to injected current and synaptic inputs. Measurements were made from the distal dendrites.

Results

It was observed that dendritic calcium transients were significantly enhanced by KIR current inactivation (Figure 1). For instance, inKIR cell when compared with non-inKIR cell had dendritic calcium transient peaks higher by as much as 93% in response to an injected current of 0.25 nA in the distal dendrite (Figure 1A). Though this difference decreased with higher currents, still the calcium peak remained higher for the inKIR cell by at least 10% (Figure 1B). The enhanced calcium influx (by up to 51%) was present even when the injected currents were matched for firing frequency. Similar results were obtained with synaptic inputs.

Figure 1
figure1

Calcium transients in non-inK IR and inK IR cell dendrites.

Discussion

The facilitatory effect of KIR current inactivation on dendritic calcium influx appears to be mediated through action potential firing frequency and their timing. In view of the reports that dendritic intracellular calcium levels influence cortico-striatal input plasticity [3], our findings suggest that KIR current inactivation may significantly modulate synaptic plasticity.

References

  1. 1.

    Mermelstein PG, Song W, Tkatch T, Yan Z, Surmeier DJ: Inwardly rectifying potassium (IRK) currents are correlated with IRK subunit expression in rat nucleus accumbens medium spiny neurons. J Neurosci. 1998, 18: 6650-6661.

  2. 2.

    Steephen J, Manchanda R: Differences in biophysical properties of nucleus accumbens medium spiny neurons emerging from inactivation of inward rectifying potassium currents (Abstract). BMC Neurosci. 2007, 8: 116-10.1186/1471-2202-8-S2-P116.

  3. 3.

    Kerr JND, Plenz D: Action potential timing determines dendritic calcium during striatal up-states. J Neurosci. 2004, 24: 877-8852. 10.1523/JNEUROSCI.4475-03.2004.

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Author information

Correspondence to John Eric Steephen.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Keywords

  • Calcium Influx
  • Facilitatory Effect
  • Firing Frequency
  • Synaptic Input
  • Ventral Striatum