視覚野NMDA受容体非依存性長期増強の誘発にはT型Ca²⁺チャネルの活性化が必要である

抄録

We previously reported that, when continued for 15 minutes, 2 Hz stimulation induced NMDA receptor-independent LTP at excitatory synapses in rat visual cortex. This LTP occurred during the critical period for visual response plasticity, but not in adulthood. LTP induction was blocked by 50 μM Ni²⁺, suggesting that it requires T or R type Ca²⁺ channel activation. To determine which one of these channels is responsible for the induction, we used blockers for T and R type Ca²⁺ channels. Extracellular field potentials evoked by layer 4 stimulation were recorded from layer 2/3 in visual cortical slices prepared from rats at postnatal 21-30 days. LTP was blocked by 3 μM Mibefradil, which blocks T type Ca²⁺ channels potently although it also affects some other channels including R type Ca²⁺ channels. Kurtoxin (250 nM), which blocks T type, but not R type, Ca²⁺ channels, also abolished LTP induction. In contrast, in the presence of a high dose (500 nM) of the R type Ca²⁺ channel blocker SNX-482, LTP occurred in the same way as in control. In addition, we recorded Ca²⁺ channel currents from layer 2/3 pyramidal cells under a pharmacological blockade of P/Q, N and L type Ca²⁺ channels. Ca²⁺ currents evoked by voltage steps from -100 to -40 mV were sensitive to 50 μM Ni²⁺ but not 10 μM Cd²⁺, indicating that they were generated by T type Ca²⁺ channels. We found that Ni²⁺-sensitive Ca²⁺ currents decreased developmentally in parallel with LTP incidence. These results suggest that T type Ca²⁺ channels are responsible for the induction of NMDA receptor-independent LTP. [Jpn J Physiol 55 Suppl:S147 (2005)]