Potassium channels for high-frequency action potential generation in GABAergic interneurons of Rat Hippocampus

Using the nucleated patch configuration that allowed me to investigate somatic ion channels under ideal voltage-clamp conditions, I started to examine the functional properties of Kv channels expressed in orien-alveus (OA) interneurons in the hippocampal CA1 region, a major class of dendritic inhibitory interneuron. The main results are as follows. First, the macroscopic K+ current in OA interneurons consists mainly of a fast delayed rectifier (57 ± 5), a slow delayed rectifier (25 ± 6), and an A-type component (19 ± 2). Second, I have found that the fast delayed rectifier K+ channel is selectively modulated by the cAMP pathway, presumably via PKA-mediated phosphorylation. Third, single-cell RT-PCR showed that the subunit composition of the Kv channels in OA interneurons appears to be unique. Fast delayed rectifier K+ current in OA interneurons is mediated predominantly by Kv3.2 homomeric channels, whereas the A-type current is mediated exclusively by Kv4.3 homomers. OA interneurons typically express only a single type of subunit of the same subfamily, suggesting preferential assembly of homomeric rather than heteromeric channels. <br>In the second part of experiments, I used the dynamic-clamp technique to decipher even more precisely the way Kv3 channels in OA interneurons facilitate FS phenotype. The results showed that Kv3 channels are necessary and sufficient for FS. They demonstrate that fast and optimized deactivation kinetics, high activation threshold, and the absence of inactivation of Kv3 are essential for high-frequency repetitive activity. Conversely, they provide direct evidence for causal links between low activation threshold and adaptation, as well as between inactivation and AP broadening. Thus, my results contribute to the understanding of the complexity of AP patterns in central neurons.

Author dc:creator

• Lien, Cheng-Chang

Contributors dc:contributor

• Jonas, Peter

• Patch-clamp technique
• Single-cell RT-PCR
• Hodgkin-Huxley-type model
• Dynamic-clamp technique

Repository record source_url

https://freidok.uni-freiburg.de/data/749

OAI identifier oai:identifier

oai:freidok.uni-freiburg.de:749