Distinct perinatal features of the hyperpolarization-activated non-selective cation current I(h) in the rat cortical plate.

Arne Battefeld, Nino Rocha, Konstantin Stadler, Anja U Bräuer, Ulf Strauss
Neural Dev. 2012-01-01; 7(1): 21
DOI: 10.1186/1749-8104-7-21

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1. Neural Dev. 2012 Jun 13;7:21. doi: 10.1186/1749-8104-7-21.

Distinct perinatal features of the hyperpolarization-activated non-selective
cation current I(h) in the rat cortical plate.

Battefeld A(1), Rocha N, Stadler K, Bräuer AU, Strauss U.

Author information:
(1)Institute of Cell Biology and Neurobiology, Center for Anatomy, Charité –
Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.

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.

DOI: 10.1186/1749-8104-7-21
PMCID: PMC3518177
PMID: 22694806 [Indexed for MEDLINE]

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