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Voltage–activated sodium channels amplify inhibition in neocortical pyramidal neurons

Abstract

Inhibitory postsynaptic potentials (IPSPs) in neocortical pyramidal neurons are increased in duration and amplitude at depolarized membrane potentials. This effect was not due to changes in the time course of the underlying synaptic current. The role of postsynaptic voltage–activated channels was investigated by mimicking the voltage change that occurs during an IPSP with current injections. The peak and integral of these 'simulated' IPSPs increased during depolarization of the membrane potential in a tetrodotoxin–sensitive manner. This amplification presumably occurs as the hyperpolarization associated with IPSPs turns off sodium channels that are tonically active at depolarized membrane potentials. IPSP amplification increased the ability of IPSPs to inhibit action potential firing and promoted IPSP–induced action potential synchronization.

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Figure 1: Effect of membrane potential on evoked IPSPs.
Figure 2: Effect of membrane potential on evoked IPSCs.
Figure 3: Generation of simulated IPSPs.
Figure 4: Effects of membrane potential and TTX on simulated IPSPs.
Figure 5: Effect of QX–314 on evoked IPSPs.
Figure 6: Effect of IPSP amplitude and duration.
Figure 7: Effect of IPSP amplification on action potential firing.

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Acknowledgements

I thank J. Bekkers and S. Williams for discussions and comments on an earlier version of the manuscript. This work was supported by an Australian Research Council QEII Research Fellowship, the Human Frontiers Science Program and the Wellcome Trust.

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Correspondence to Greg Stuart.

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Stuart, G. Voltage–activated sodium channels amplify inhibition in neocortical pyramidal neurons. Nat Neurosci 2, 144–150 (1999). https://doi.org/10.1038/5698

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