Differential effects of Kv7 (M–) channels on synaptic integration in distinct subcellular compartments of rat hippocampal pyramidal neurons

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Abstract

Non–technical summary

Ion channels are pores that allow the exchange of molecules across cell membranes. In nerve cells (neurons) of the hippocampus (a brain region involved in learning and memory), the potassium KV7 channel is present predominantly in the cell body (the soma) and in its axon, a projection from the cell body that produces brief electrical signals known as action potentials. We have previously shown that axonal KV7 channels control action potential initiation and so regulate cell excitability. However, cells also receive inputs from other cells connected to them, resulting in longer lasting electrical signals known as synaptic potentials. In this study, we show that only somatic KV7 channels influence synaptic potential shapes and summation, whereas axonal channels increase the ability of synaptic potentials to generate action potentials. Hence, axonal and somatic KV7 channels differentially contribute to information processing within hippocampal neurons, which may be important for processes such as cognition

The KV7/M–current is an important determinant of neuronal excitability and plays a critical role in modulating action potential firing. In this study, using a combination of electrophysiology and computational modelling, we show that these channels selectively influence peri–somatic but not dendritic post–synaptic excitatory synaptic potential (EPSP) integration in CA1 pyramidal cells. KV7/M–channels are highly concentrated in axons. However, the competing peptide, ankyrin G binding peptide (ABP) that disrupts axonal KV7/M–channel function, had little effect on somatic EPSP integration, suggesting that this effect was due to local somatic channels only. This interpretation was confirmed using computer simulations. Further, in accordance with the biophysical properties of the KV7/M–current, the effect of somatic KV7/M–channels on synaptic potential summation was dependent upon the neuronal membrane potential. Somatic KV7/M–channels thus affect EPSP–spike coupling by altering EPSP integration. Interestingly, disruption of axonal channels enhanced EPSP–spike coupling by lowering the action potential threshold. Hence, somatic and axonal KV7/M–channels influence EPSP–spike coupling via different mechanisms. This may be important for their relative contributions to physiological processes such as synaptic plasticity as well as patho–physiological conditions such as epilepsy.

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