Poster presentation | Open | Published:
KAchannels reduce dendritic depolarization from synchronized synaptic input: implication for neural processing and epilepsy
BMC Neurosciencevolume 9, Article number: P45 (2008)
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 e.g., epileptogenic activity is characterized by excess spiking at high synchronicity. Furthermore with regard to neuronal excitability, synchronous input is the most effective input. 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 . An objective of this work was to investigate if KAcould suppress synchronized synaptic input while minimally suppressing semi-synchronous input.
We used a cell model of a hippocampal CA1 pyramidal neuron based on Migliore et al . It is composed of 566 compartments with Na, Kdr and KA -type currents of Hodgkin-Huxley type. Ten synaptic inputs were added on a medial compartment. The simulation was run for 1.5 s and repeated 15 times with different levels of synchronicity. To estimate the standard deviation, the procedure was repeated 20 times with different random seeds.
Our model shows that KA differentially suppresses responses to varying levels of input synchrony. The study indicates that the selectivity of KA originates from its dynamic interaction between fast activation and slower inactivation in response to the waveform of a synchronized input, in the voltage region: -60 to -30 mV.
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: 245-53. 10.1016/j.nbd.2006.07.001.
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-Kα and pandinustoxin-Kα. Epilepsy Res. 1999, 34: 177-186. 10.1016/S0920-1211(98)00111-9.
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.