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KA channels suppress cellular responses to fast ripple activity – implications for epilepsy
BMC Neuroscience volume 10, Article number: P226 (2009)
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 . 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  and a highly selective blocker of KA induced seizures . 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.
We used a cell model of a hippocampal CA1 pyramidal neuron based on . 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 . According to , 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.
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.
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.
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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). https://doi.org/10.1186/1471-2202-10-S1-P226
- Temporal Lobe Epilepsy
- Synaptic Input
- Mesial Temporal Lobe Epilepsy
- Temporal Lobe Epilepsy Patient
- Field Oscillation