HCN1 subunits contribute to the kinetics of I(h) in neonatal cortical plate neurons.
Devel Neurobio. 2013-08-20; 73(10): 785-797
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1. Dev Neurobiol. 2013 Oct;73(10):785-97. doi: 10.1002/dneu.22104. Epub 2013 Aug 20.
HCN1 subunits contribute to the kinetics of I(h) in neonatal cortical plate
Stoenica L(1), Wilkars W, Battefeld A, Stadler K, Bender R, Strauss U.
(1)Institute of Cell Biology & Neurobiology, Charité-Universitätsmedizin, Berlin,
The distribution of ion channels in neurons regulates neuronal activity and
proper formation of neuronal networks during neuronal development. One of the
channels is the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel
constituting the molecular substrate of hyperpolarization-activated current
(I(h)). Our previous study implied a role for the fastest activating subunit HCN1
in the generation of Ih in rat neonatal cortical plate neurons. To better
understand the impact of HCN1 in early neocortical development, we here performed
biochemical analysis and whole-cell recordings in neonatal cortical plate and
juvenile layer 5 somatosensory neurons of HCN1(-/-) and control HCN1(+/+) mice.
Western Blot analysis revealed that HCN1 protein expression in neonatal cortical
plate tissue of HCN(+/+) mice amounted to only 3% of the HCN1 in young adult
cortex and suggested that in HCN1(-/-) mice other isoforms (particularly HCN4)
might be compensatory up-regulated. At the first day after birth, functional
ablation of the HCN1 subunit did not affect the proportion of Ih expressing
pyramidal cortical plate neurons. Although the contribution of individual subunit
proteins remains open, the lack of HCN1 markedly slowed the current activation
and deactivation in individual I(h) expressing neurons. However, it did not
impair maximal amplitude/density, voltage dependence of activation, and cAMP
sensitivity. In conclusion, our data imply that, although expression is
relatively low, HCN1 contributes substantially to I(h) properties in individual
cortical plate neurons. These properties are significantly changed in HCN1(-/-),
either due to the lack of HCN1 itself or due to compensatory mechanisms.
Copyright © 2013 Wiley Periodicals, Inc.
PMID: 23821600 [Indexed for MEDLINE]