TY - JOUR
T1 - Cloning and localization of the hyperpolarization-activated cyclic nucleotide-gated channel family in rat brain
AU - Monteggia, Lisa M
AU - Eisch, Amelia J
AU - Tang, Michael D.
AU - Kaczmarek, Leonard K.
AU - Nestler, Eric J.
N1 - Funding Information:
We are grateful to Dr. Suzanne Numan for help with the in situ hybridization technique. We thank Drs. George Aghajanian, Anita Luthi and David A. McCormick for helpful discussions and Yevette Clancy for excellent technical support. This work is supported by grants from the National Institute on Drug Abuse and the National Institute of Mental Health, and by the Abraham Ribicoff Research Facilities of the Connecticut Mental Health Center, State of Connecticut Department of Mental Health and Addiction Services.
PY - 2000/9/30
Y1 - 2000/9/30
N2 - Rhythmic firing in brain and heart is mediated by pacemaker channels that are activated by hyperpolarization and regulated directly by cyclic nucleotides. Recent work has identified a new gene family that encodes such channels, which are termed hyperpolarization-activated, cyclic nucleotide- gated (HCN) channels. In this study, we report the molecular cloning and localization by in situ hybridization of HCN1-4 in adult rat brain. The rat HCN1-4 clones show high homology to the deduced amino acid sequence of the mouse channels (>97% identity). The mRNA expression of the four channels in adult brain was evaluated in a systematic manner from the olfactory bulb to lower brain stem nuclei. Each mRNA demonstrated a unique pattern of distribution. HCN1 expression is highly enriched in cerebral cortex, hippocampus, cerebellum, and facial motor nucleus; HCN2 is highly abundant in mamillary bodies, pontine nucleus, ventral cochlear nucleus, and nucleus of the trapezoid body; HCN3 expression is most pronounced in supraoptic nucleus of hypothalamus; and HCN4 expression is most abundant in medial habenula and anterior and principal relay nuclei of the thalamus. These variations in regional specificity of HCN channels could generate important differences in neuronal pacemaker activity across brain systems. (C) 2000 Elsevier Science B.V.
AB - Rhythmic firing in brain and heart is mediated by pacemaker channels that are activated by hyperpolarization and regulated directly by cyclic nucleotides. Recent work has identified a new gene family that encodes such channels, which are termed hyperpolarization-activated, cyclic nucleotide- gated (HCN) channels. In this study, we report the molecular cloning and localization by in situ hybridization of HCN1-4 in adult rat brain. The rat HCN1-4 clones show high homology to the deduced amino acid sequence of the mouse channels (>97% identity). The mRNA expression of the four channels in adult brain was evaluated in a systematic manner from the olfactory bulb to lower brain stem nuclei. Each mRNA demonstrated a unique pattern of distribution. HCN1 expression is highly enriched in cerebral cortex, hippocampus, cerebellum, and facial motor nucleus; HCN2 is highly abundant in mamillary bodies, pontine nucleus, ventral cochlear nucleus, and nucleus of the trapezoid body; HCN3 expression is most pronounced in supraoptic nucleus of hypothalamus; and HCN4 expression is most abundant in medial habenula and anterior and principal relay nuclei of the thalamus. These variations in regional specificity of HCN channels could generate important differences in neuronal pacemaker activity across brain systems. (C) 2000 Elsevier Science B.V.
KW - Hyperpolarization-activated channel
KW - I(h)
KW - In situ hybridization
KW - Molecular cloning
KW - Pacemaker activity
KW - Rat
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U2 - 10.1016/S0169-328X(00)00155-8
DO - 10.1016/S0169-328X(00)00155-8
M3 - Article
C2 - 11000485
AN - SCOPUS:0034734788
SN - 0169-328X
VL - 81
SP - 129
EP - 139
JO - Molecular Brain Research
JF - Molecular Brain Research
IS - 1-2
ER -