Distinct perinatal features of the hyperpolarization-activated non-selective cation current Ih in the rat cortical plate

Neural Development

Ulf Strauss²  Anja U Bräuer³  Konstantin Stadler³  Nino Rocha²  Arne Battefeld¹ 

[1] Netherlands Institute for Neuroscience, Meibergdreef 47, 1105, BA, Amsterdam, The Netherlands;University Rostock, Neurological Clinic, Gehlsheimer Strasse 20, 18147, Rostock, Germany;Institute of Cell Biology and Neurobiology, Center for Anatomy, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany

关键词: Electrophysiology;    Neuronal development;    HCN;   

Others  :  807547
DOI  :  10.1186/1749-8104-7-21

 received in 2012-04-15, accepted in 2012-05-10,  发布年份 2012

【 摘 要 】

Background

During neocortical development, multiple voltage- and ligand-gated ion channels are differentially expressed in neurons thereby shaping their intrinsic electrical properties. One of these voltage-gated ion channels, the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel and its current I_h, is an important regulator of neuronal excitability. Thus far, studies on an early I_h appearance in rodent neocortex are missing or conflicting. Therefore, we focused our study on perinatal neocortical I_h and its properties.

Results

In the perinatal rat neocortex we observed a rapid increase in the number of neurons exhibiting I_h. Perinatal I_h had unique properties: first, a pronounced cAMP sensitivity resulting in a marked shift of the voltage sufficient for half-maximum activation of the current towards depolarized voltages and second, an up to 10 times slower deactivation at physiological membrane potentials when compared to the one at postnatal day 30. The combination of these features was sufficient to suppress membrane resonance in our in silico and in vitro experiments. Although all four HCN subunits were present on the mRNA level we only detected HCN4, HCN3 and HCN1 on the protein level at P0. HCN1 protein at P0, however, appeared incompletely processed. At P30 glycosilated HCN1 and HCN2 dominated. By in silico simulations and heterologous co-expression experiments of a ‘slow’ and a ‘fast’ I_h conducting HCN channel subunit in HEK293 cells, we mimicked most characteristics of the native current, pointing to a functional combination of subunit homo- or heteromeres.

Conclusion

Taken together, these data indicate a HCN subunit shift initiated in the first 24 hours after birth and implicate a prominent perinatal role of the phylogenetically older HCN3 and/or HCN4 subunits in the developing neocortex.

【 授权许可】

   
2012 Battefeld et al.; licensee BioMed Central Ltd.

【 图 表 】

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