PubMed 23821600

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: HCN1 , HCN3 , HCN4 , Kir6.2 , Slo1

Title: HCN1 subunits contribute to the kinetics of Ih in neonatal cortical plate neurons.

Authors: Luminita Stoenica, Wiebke Wilkars, Arne Battefeld, Konstantin Stadler, Roland Bender, Ulf Strauss

Journal, date & volume: Dev Neurobiol, 2013 Jul 2 , ,

PubMed link:

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.