Physiological roles of Kv2 channels in entorhinal cortex layer II stellate cells revealed by Guangxitoxin-1E

Abstract

The medial entorhinal cortex (mEC) is strongly involved in spatial navigation, memory, dementia and epilepsy. Although potassium channels shape neuronal activity, their roles in mEC are largely unknown. We used the new Kv2 blocker Guangxitoxin-1E (GTx, 10–100 nm) in rat brain slices to investigate Kv2 channel functions in mEC layer II stellate cells (SCs). These neurons project to the hippocampus and are thought to be grid cells representing space. Voltage clamp recordings from SCs nucleated patches showed that GTx inhibited a delayed rectifier K⁺ current activating beyond -30 mV, but not transient, A-type current. In current clamp, GTx (1) had virtually no effect on the first action potential, but markedly slowed repolarization of late spikes during repetitive firing; (2) enhanced the after-depolarization (ADP); (3) reduced fast and medium after-hyperpolarizations (fAHPs, mAHPs); (4) strongly enhanced burst firing and increased excitability at moderate spike rates, but reduced spiking at high rates; (5) reduced spike clustering and rebound potentials. The changes in bursting and excitability were related to the altered ADPs and AHPs. Kv2 channels strongly shape the activity of mEC stellate cells, by affecting spike repolarization, after-potentials, excitability and spike patterns. GTx is a useful tool and may serve to further elucidate Kv2 channel functions in neurons. We conclude that Kv2 channels in mEC SCs are important determinants of intrinsic properties that allow these neurons to produce spatial representation. Our results may also be important for accurate modelling of grid cells.

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