Differential roles of Kv4.1 and Kv4.2 channels in excitatory postsynaptic responses in the hippocampus

Abstract

A-type K+ channel is important in the integration of subthreshold synaptic potentials and it is suggested that signaling mechanisms by regulation of A-type K+ channel could profoundly influence neuronal excitability. Among the Kv4 family, the intrinsic property of Kv4.1 and Kv4.2 channels are widely studied. Until today, however, the contribution of A-type K+ channel in synaptic plasticity remains unknown. The effectiveness of inhibition of K+ channel in synaptic modification is compared in DG and CA1. 50 Hz train stimulus applied either perforant path-DG granule cell or Schaffer collateral-CA1 pyramidal cell pathways. I observed synaptic response by using an antibody to Kv4.1/Kv4.2 and found that Kv4.2 channel has the correlation with synaptic plasticity. My data demonstrates that inhibition of Kv4.2 induce enhancement with synaptic plasticity, whereas an anti-Kv4.1 antibody does not affect. This form of plasticity is different from the general long-term plasticity which was studied before. The mechanisms underlying the effect on synaptic plasticity were investigated. It was observed that NMDA receptor blocker, APV, partially blocked potentiation in DG. However, a complete blockade of the potentiation occurred when nimodipine (L-type voltage-gated Ca2+ channel antagonist) was applied. In addition, PKC plays a crucial role in intracellular signaling cascades and its mechanisms thought to be involved in synaptic plasticity. My results support the evidence of distinct density and distribution about Kv4.1 / Kv4.2 in DG and CA1 of the hippocampus. Furthermore, in this study, I clearly show that that synaptic plasticity that associated with Kv4.2 which is distinct from general synaptic plasticity and its mechanism.