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

Christoph Hönigsperger, Maximiliano J. Nigro, Johan F. Storm
2016 Journal of Physiology  
23 24 Word count: 5605 25 26 27 28 29 30 31 Key points summary 1 2  Kv2 channels underlie delayed-rectifier potassium currents in various neurons, 3 but their physiological roles often remain elusive. Virtually nothing is known 4 about Kv2 channel functions in medial entorhinal cortex (mEC) neurons, which 5 are involved in representing space, memory formation, epilepsy and dementia. 6  Stellate cells in layer II of the mEC project to the hippocampus and are thought 7 to be space-representing
more » ... rid cells. We used the new Kv2 blocker 8 Guangxitoxin-1E (GTx) to study Kv2 functions in these neurons. 9  Voltage clamp recordings from mEC stellate cells in rat brain slices showed 10 that GTx inhibited a delayed-rectifier K + current, but not transient A-type 11 current. 12  In current clamp, GTx had multiple effects: (1) increasing excitability and 13 bursting at moderate spike rates but reducing firing at high rates, (2) 14 enhancing after-depolarizations (ADPs), (3) reducing the fast and medium 15 after-hyperpolarizations (fAHPs, mAHPs), (4) broadening action potentials, (5) 16 reducing spike clustering. 17  GTx is a useful tool for studying Kv2 channels, and their functions in neurons. Abstract 1 The medial entorhinal cortex (mEC) is strongly involved in spatial navigation, memory, 2 dementia and epilepsy. Although potassium channels shape neuronal activity, their 3 roles in mEC are largely unknown. We used the new Kv2 blocker Guangxitoxin-1E 4 (GTx, 10-100 nM) in rat brain slices to investigate Kv2 channel functions in mEC 5 layer II stellate cells (SCs). These neurons project to the hippocampus and are 6 thought to be grid cells representing space. Voltage clamp recordings from SCs 7 nucleated patches showed that GTx inhibited a delayed rectifier K + current activating 8 beyond -30 mV, but not transient, A-type current. In current clamp, GTx (1) had 9 virtually no effect on the first action potential, but markedly slowed repolarization of 10 late spikes during repetitive firing; (2) enhanced the after-depolarization (ADP); (3) 11 reduced fast and medium after-hyperpolarizations (fAHPs, mAHPs); (4) strongly 12 enhanced burst firing and increased excitability at moderate spike rates, but reduced 13 spiking at high rates; (5) reduced spike clustering and rebound potentials. The 14 changes in bursting and excitability were related to the altered ADPs and AHPs. Kv2 15 channels strongly shape the activity of mEC stellate cells, by affecting spike 16 repolarization, after-potentials, excitability and spike patterns. GTx is a useful tool 17 and may serve to further elucidate Kv2 channel functions in neurons. We conclude 18 that Kv2 channels in mEC SCs are important determinants of intrinsic properties that 19 allow these neurons to produce spatial representation. Our results may also be 20 important for accurate modelling of grid cells. 21 22 23 Word count: 205 24 25 26 27 28 29 30 31 32 33
doi:10.1113/jp273024 pmid:27562026 fatcat:o72perdbtnfzjddkouq3uqfyr4