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KA channels suppress cellular responses to fast ripple activity – implications for epilepsy

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Background

During cognitive tasks, synchrony of neural activity varies and is correlated with performance. There may however be an upper limit to the level of normal synchronicity and epileptogenic activity is characterized by excess spiking at high synchronicity. Very high field oscillations (fast ripples), in the range of 250–600 Hz, have been recorded from patients with mesial temporal lobe epilepsy [1]. Furthermore, in epilepsy an A-type potassium channel (KA) has been implicated. More specifically, a mutation in a KA gene was found in a temporal lobe epilepsy patient [2] and a highly selective blocker of KA induced seizures [3]. In previous work we have showed that KA can suppress synchronized synaptic input to a neuron while minimally suppressing semi-synchronous input. As high frequency implies high synchronicity we set out to investigate if KA could suppress the cellular response from fast ripple activity.

Methods

We used a cell model of a hippocampal CA1 pyramidal neuron based on [4]. It is a detailed compartment model with Na, Kdr and KA-type currents of Hodgkin-Huxley type. The high frequency of fast ripples has been hypothesis to occur from combining two ripples with lower frequency [5]. According to [6], only 11% of the neurons participating in a ripple are activated at each ripple. Due to these two factors we used 60 Hz as the frequency of individual neurons. In a fast ripple, the 50 synaptic inputs were activated simultaneously and in control/desynchronized the input were evenly distributed in time.

Results

KA channels suppress cellular responses to fast ripple activity. The left figures of Figure 1 represent the simulation KA present and the right with KA absent. Top figures represent fast ripple activity and bottom figures the case when the input is control/desynchronized. Note that when KA is present there is no spike activity from fast ripple input even though it is present in control/desynchronized.

figure1

Figure 1

Discussion

Our model shows that KA can prevent the cell form getting activated by fast ripple activity. Understanding how KA can reduce synchronized and fast ripple activity can provide insight in how epileptic drug work or suggests new drugs targeting KA.

References

  1. 1.

    Engel J, Bragin A, Staba R, Mody I: High-frequency oscillations: What is normal and what is not?. Epilepsia. 2008 in press.

  2. 2.

    Singh B, Ogiwara I, Kaneda M, Tokonami N, Mazaki E, Baba K, Matsuda K, Inoue Y, Yamakawa K: A Kv4.2 truncation mutation in a patient with temporal lobe epilepsy. Neurobiol Dis. 2006, 24: 245-253. 10.1016/j.nbd.2006.07.001.

  3. 3.

    Juhng K, Kokate T, Yamaguchi S, Kim B, Rogowski R, Blaustein M, Rogawski M: Induction of seizures by the potent K+ channel-blocking scorpion venom peptidetoxins tityustoxin-K- and pandinustoxin-K-. Epilepsy Res. 1999, 34: 177-186. 10.1016/S0920-1211(98)00111-9.

  4. 4.

    Migliore M, Hoffman D, Magee J, Johnston D: Role of an A-type K+ conductance in the back-propagation of action potentials in the dendrites of hippocampal pyramidal neurons. J Comput Neurosci. 1999, 7: 5-15. 10.1023/A:1008906225285.

  5. 5.

    Staley KJ: Neurons skip a beat during fast ripples. Neuron. 2007, 55: 828-830. 10.1016/j.neuron.2007.09.005.

  6. 6.

    Ylinen A, Bragin A, Nádasdy Z, Jandó G, Szabó I, Sik A, Buzsáki G: Sharp wave-associated high-frequency oscillation (200 Hz) in the intact hippocampus: network and intracellular mechanisms. J Neurosci. 1995, 15: 30-46.

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Author information

Correspondence to Erik Fransén.

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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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Tigerholm, J., Fransén, E. KA channels suppress cellular responses to fast ripple activity – implications for epilepsy. BMC Neurosci 10, P226 (2009) doi:10.1186/1471-2202-10-S1-P226

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Keywords

  • Temporal Lobe Epilepsy
  • Synaptic Input
  • Mesial Temporal Lobe Epilepsy
  • Temporal Lobe Epilepsy Patient
  • Field Oscillation