Differential Distribution of Four Hyperpolarization-Activated Cation Channels in Mouse Brain

Abstract

Hyperpolarization-activated cation currents, termed I(h), are observed in a variety of neurons. Four members of a gene family encoding hyperpolarization-activated cyclic-nucleotide-gated cation channels (HCN1-4) have been cloned. The regional expression and cellular localization of the four HCN channel types in mouse brain was investigated using in situ hybridization. The expression of HCN1 was restricted to the olfactory bulb, cerebral cortex, hippocampus, superior colliculus and cerebellum. In contrast, HCN2 transcripts were found at high levels nearly ubiquitously in the brain, and the strongest signals were seen in the olfactory bulb, hippocampus, thalamus and brain stem. HCN3 was uniformly expressed at very low levels throughout the brain. Finally, HCN4 transcripts were prominently expressed selectively in the thalamus and olfactory bulb. Some neurons expressed two or more HCN channel transcripts including hippocampal pyramidal neurons (HCN1, HCN2 and low levels of HCN 4) and thalamic relay neurons (HCN2 and HCN4). Our results demonstrate that each HCN channel transcript has a unique distribution in the brain. Furthermore, they suggest that the heterogeneity of neuronal I(h) may be, at least in part, due to the differential expression of HCN channel genes.

Immunohistochemical localization of Ih channel subunits, HCN1–4, in the rat brain

“…Immunoreactivity for HCN2 has a very widespread distribution throughout the brain. The distribution of HCN-LI is more extensive than that of their mRNAs indicated by previous in situ hybridization studies (Moosmang et al, 1999;Monteggia et al, 2000;Santoro et al, 2000). In many regions, we found a strong overlap among the …”

“…In situ hybridization studies demonstrate that all four HCN isoforms are expressed in the adult mouse and rat brains with different regional expression patterns (Ludwig et al, 1998;Santoro et al, 1998;Moosmang et al, 1999;Monteggia et al, 2000;Santoro et al, 2000;Bender et al, 2001). …”

Characterization of Rebound Depolarization in Neurons of the Rat Medial Geniculate Body In Vitro

“…HCN Channels Regulate RD Mainly by Changing the Resting Membrane Potential HCN channels have a high level of distribution in different types of neurons in the MGB [42,43]. Because of masking interference from Kir channels, we seldom recorded the sag phenomenon in MGB neurons.…”

Formation of heteromeric hyperpolarization-activated cyclic nucleotide-gated (HCN) channels in the hippocampus is regulated by developmental seizures

“…HCN4 is expressed almost exclusively in subcortical regions, whereas levels of HCN3 expression within neurons are generally low (Bender et al, 2001;Moosmang et al, 1999;Santoro et al, 2000). As described for other members of the voltage-gated cation channel family, four HCN subunits assemble to form a channel (for recent reviews, see Robinson and Siegelbaum, 2003;Santoro and Baram, 2003).…”

“…Of the four characterized genes encoding HCN channels, two (HCN1 and 2) are substantially expressed in rodent hippocampus (Bender et al, 2001;Moosmang et al, 1999;Santoro et al, 2000) and both isoforms can reside in a single neuron (Brewster et al, 2002;Franz et al, 2000). HCN4 is expressed almost exclusively in subcortical regions, whereas levels of HCN3 expression within neurons are generally low (Bender et al, 2001;Moosmang et al, 1999;Santoro et al, 2000).…”