Cloning and localization of the hyperpolarization-activated cyclic nucleotide-gated channel family in rat brain

Rhythmic firing in brain and heart is mediated by pacemaker channels that a re activated by hyperpolarization and regulated directly by cyclic nucleoti des. Recent work has identified a new gene family that encodes such channel s, which are termed hyperpolarization-activated, cyclic nucleotide-gated (H CN) channels. In this study, we report the molecular cloning and localizati on by in situ hybridization of HCN1-4 in adult rat brain. The rat HCN1-4 cl ones show high homology to the deduced amino acid sequence of the mouse cha nnels (>97% identity). The mRNA expression of the four channels in adult br ain was evaluated in a systematic manner from the olfactory bulb to lower b rain stem nuclei. Each mRNA demonstrated a unique pattern of distribution. HCN1 expression is highly enriched in cerebral cortex, hippocampus, cerebel lum, and facial motor nucleus; HCN2 is highly abundant in mamillary bodies, pontine nucleus, ventral cochlear nucleus, and nucleus of the trapezoid bo dy; NCN3 expression is most pronounced in supraoptic nucleus of hypothalamu s; and HCN4 expression is most abundant in medial habenula and anterior and principal relay nuclei of the thalamus. These variations in regional speci ficity of HCN channels could generate important differences in neuronal pac emaker activity across brain systems. (C) 2000 Elsevier Science B.V. All ri ghts reserved.