Sammendrag
Potassium channels of the KCNQ family are widely expressed in the mammalian brain. In hippocampal pyramidal cells, such channels (M-channels) underlie medium afterhyperpolarization (mAHP) and early spike frequency adaptation and may regulate synaptic plasticity. Immunhistochemical studies suggest that M-channels are expressed both pre- and postsynapticly in area CA1. To assess the role of M-channels in synaptic transmission, integration and excitability, we examined synaptic responses at Schaeffer collateral synapses in area CA1 of rat hippocampal slices. We stimulated presynaptic axons in str.radiatum while recording (e.c.) field potentials near the Schaeffer CA1 synapses in str.radiatum, and in the CA1 soma layer, and intracellular (i.c.) somatic responses. Blockade of M-channels by linopirdine or XE 991 did not significantly change the e.c. presynaptic fiber volley amplitudes or duration, suggesting that the number of activated axons is not substantially changed. However, M-channel blockade enhanced action potential (AP) discharge evoked by excitatory postsynaptic potentials (EPSPs) as well as the AP frequency in response to depolarizing current injection, even when the background membrane potential was manually clamped at a constant level during i.c. recording. In contrast, when the postsynaptic M-channels were blocked by loading the cells with Cs+ ions, no change in synaptic efficacy or AP discharge was observed, suggesting that presynaptic M-channels did not affect transmitter release under these conditions. These results suggest that postsynaptic M-channels regulate the ability of excitatory synaptic input to evoke action potentials in hippocampal CA1 pyramidal cells. The increase in spike discharge following M-channel blockade probably reflects increased somatic excitability, caused by suppression of M-channels at the initial segment and soma of the CA1 pyramidal cells.
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