Single-cell mRNA expression of HCN1 correlates with a fast gating phenotype of hyperpolarization-activated cyclic nucleotide-gated ion channels (Ih) in central neurons

TY - JOUR

T1 - Single-cell mRNA expression of HCN1 correlates with a fast gating phenotype of hyperpolarization-activated cyclic nucleotide-gated ion channels (Ih) in central neurons

AU - Franz, O

AU - Liss, B

AU - Neu, A

AU - Roeper, J

PY - 2000/8/1

Y1 - 2000/8/1

N2 - Hyperpolarization-activated currents (Ih) are key players in shaping rhythmic neuronal activity. Although candidate genes for Ih channels have been cloned (HCN1-HCN4), the subunit composition of different native Ih channels is unknown. We used a combined patch-clamp and qualitative single-cell reverse transcription multiplex polymerase chain reaction (RT-mPCR) approach to analyse HCN1-4 coexpression profiles in four neuronal populations in mouse CNS. Coexpression of HCN2, HCN3 and HCN4 mRNA was detected in single neurons of all four neuronal cell types analysed. In contrast, HCN1 mRNA was detected in neocortical and hippocampal pyramidal neurons but not in dopaminergic midbrain and thalamocortical neurons. HCN1 expression was correlated with significantly faster activation kinetics on the level of individual neurons. Semiquantitative single-cell RT-mPCR analysis demonstrated that HCN1 mRNA expression is at least eightfold higher in cortical neurons than subcortical neurons. We show that single neurons possess complex coexpression patterns of Ih candidate genes. Alternative expression of HCN1 is likely to be an important molecular determinant to generate the different neuronal Ih channel species adapted to tune either subcortical or cortical network activity.

AB - Hyperpolarization-activated currents (Ih) are key players in shaping rhythmic neuronal activity. Although candidate genes for Ih channels have been cloned (HCN1-HCN4), the subunit composition of different native Ih channels is unknown. We used a combined patch-clamp and qualitative single-cell reverse transcription multiplex polymerase chain reaction (RT-mPCR) approach to analyse HCN1-4 coexpression profiles in four neuronal populations in mouse CNS. Coexpression of HCN2, HCN3 and HCN4 mRNA was detected in single neurons of all four neuronal cell types analysed. In contrast, HCN1 mRNA was detected in neocortical and hippocampal pyramidal neurons but not in dopaminergic midbrain and thalamocortical neurons. HCN1 expression was correlated with significantly faster activation kinetics on the level of individual neurons. Semiquantitative single-cell RT-mPCR analysis demonstrated that HCN1 mRNA expression is at least eightfold higher in cortical neurons than subcortical neurons. We show that single neurons possess complex coexpression patterns of Ih candidate genes. Alternative expression of HCN1 is likely to be an important molecular determinant to generate the different neuronal Ih channel species adapted to tune either subcortical or cortical network activity.

KW - Animals

KW - Brain

KW - Cells, Cultured

KW - Cyclic Nucleotide-Gated Cation Channels

KW - Dendrites

KW - Dopamine

KW - Gene Expression

KW - Hippocampus

KW - Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels

KW - Ion Channel Gating

KW - Ion Channels

KW - Membrane Potentials

KW - Mice

KW - Mice, Inbred C57BL

KW - Neocortex

KW - Nerve Tissue Proteins

KW - Neurons

KW - Nucleotides, Cyclic

KW - Patch-Clamp Techniques

KW - Phenotype

KW - Polymerase Chain Reaction

KW - Potassium Channels

KW - RNA, Messenger

KW - Thalamus

M3 - SCORING: Journal article

C2 - 10971612

VL - 12

SP - 2685

EP - 2693

JO - EUR J NEUROSCI

JF - EUR J NEUROSCI

SN - 0953-816X

IS - 8

ER -