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The Journal of Neuroscience, July 15, 2000, 20(14):5264-5275
Molecular and Functional Heterogeneity of Hyperpolarization-Activated Pacemaker Channels in the Mouse CNS
Bina Santoro1, Shan Chen2, Anita Lüthi5, Paul Pavlidis1, Gleb P. Shumyatsky1, Gareth R. Tibbs2, 3, and Steven A. Siegelbaum1, 2, 4 1 Center for Neurobiology and Behavior, Departments of 2 Pharmacology and 3 Anesthesiology, and 4 Howard Hughes Medical Institute, Columbia University, New York, New York 10032, and 5 Section of Neurobiology, Yale University, New Haven, Connecticut 06510
The hyperpolarization-activated cation current (termed Ih, Iq, or If) was recently shown to be encoded by a new family of genes, named HCN for hyperpolarization-activated cyclic nucleotide-sensitive cation nonselective. When expressed in heterologous cells, each HCN isoform generates channels with distinct activation kinetics, mirroring the range of biophysical properties of native Ih currents recorded in different classes of neurons. To determine whether the functional diversity of Ih currents is attributable to different patterns of HCN gene expression, we determined the mRNA distribution across different regions of the mouse CNS of the three mouse HCN genes that are prominently expressed there (mHCN1, 2 and 4). We observe distinct patterns of distribution for each of the three genes. Whereas mHCN2 shows a widespread expression throughout the CNS, the expression of mHCN1 and mHCN4 is more limited, and generally complementary. mHCN1 is primarily expressed within neurons of the neocortex, hippocampus, and cerebellar cortex, but also in selected nuclei of the brainstem. mHCN4 is most highly expressed within neurons of the medial habenula, thalamus, and olfactory bulb, but also in distinct neuronal populations of the basal ganglia. Based on a comparison of mRNA expression with an electrophysiological characterization of native Ih currents in hippocampal and thalamic neurons, our data support the idea that the functional heterogeneity of Ih channels is attributable, in part, to differential isoform expression. Moreover, in some neurons, specific functional roles can be proposed for Ih channels with defined subunit composition.
Key words: Ih; pacemaker channel; hippocampus; thalamus; in situ hybridization; HCN
Copyright © 2000 Society for Neuroscience 0270-6474/00/20145264-12$05.00/0
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Activation of {beta}1-Adrenoceptors Excites Striatal Cholinergic Interneurons through a cAMP-Dependent, Protein Kinase-Independent Pathway
J. Neurosci., June 15, 2003; 23(12): 5272 - 5282.
[Abstract] [Full Text] [PDF]
H. Lesso and R. A. Li
Helical Secondary Structure of the External S3-S4 Linker of Pacemaker (HCN) Channels Revealed by Site-dependent Perturbations of Activation Phenotype
J. Biol. Chem., June 13, 2003; 278(25): 22290 - 22297.
[Abstract] [Full Text] [PDF]
M. Russier, E. Carlier, N. Ankri, L. Fronzaroli, and D. Debanne
A-, T-, and H-type Currents Shape Intrinsic Firing of Developing Rat Abducens Motoneurons
J. Physiol., May 15, 2003; 549(1): 21 - 36.
[Abstract] [Full Text] [PDF]
J. C. Brumberg, F. Hamzei-Sichani, and R. Yuste
Morphological and Physiological Characterization of Layer VI Corticofugal Neurons of Mouse Primary Visual Cortex
J Neurophysiol, May 1, 2003; 89(5): 2854 - 2867.
[Abstract] [Full Text] [PDF]
A. Agmon and J. E. Wells
The Role of the Hyperpolarization-Activated Cationic Current Ih in the Timing of Interictal Bursts in the Neonatal Hippocampus
J. Neurosci., May 1, 2003; 23(9): 3658 - 3668.
[Abstract] [Full Text] [PDF]
Q.-Q. Sun, D. A. Prince, and J. R. Huguenard
Vasoactive Intestinal Polypeptide and Pituitary Adenylate Cyclase-Activating Polypeptide Activate Hyperpolarization-Activated Cationic Current and Depolarize Thalamocortical Neurons In Vitro
J. Neurosci., April 1, 2003; 23(7): 2751 - 2758.
[Abstract] [Full Text] [PDF]
S. Tanaka, N. Wu, C.-F. Hsaio, J. Turman Jr., and S. H. Chandler
Development of Inward Rectification and Control of Membrane Excitability in Mesencephalic V Neurons
J Neurophysiol, March 1, 2003; 89(3): 1288 - 1298.
[Abstract] [Full Text] [PDF]
E. Azene, T. Xue, and R. A Li
Molecular Basis of the Effect of Potassium on Heterologously Expressed Pacemaker (HCN) Channels
J. Physiol., March 1, 2003; 547(2): 349 - 356.
[Abstract] [Full Text] [PDF]
S. R. Chaplan, H.-Q. Guo, D. H. Lee, L. Luo, C. Liu, C. Kuei, A. A. Velumian, M. P. Butler, S. M. Brown, and A. E. Dubin
Neuronal Hyperpolarization-Activated Pacemaker Channels Drive Neuropathic Pain
J. Neurosci., February 15, 2003; 23(4): 1169 - 1178.
[Abstract] [Full Text] [PDF]
S. J. B. Butt, R. M. Harris-Warrick, and O. Kiehn
Firing Properties of Identified Interneuron Populations in the Mammalian Hindlimb Central Pattern Generator
J. Neurosci., November 15, 2002; 22(22): 9961 - 9971.
[Abstract] [Full Text] [PDF]
L. Sartiani, P. Bochet, E. Cerbai, A. Mugelli, and R. Fischmeister
Functional expression of the hyperpolarization-activated, non-selective cation current If in immortalized HL-1 cardiomyocytes
J. Physiol., November 15, 2002; 545(1): 81 - 92.
[Abstract] [Full Text] [PDF]
N. Tran, C. Proenza, V. Macri, F. Petigara, E. Sloan, S. Samler, and E. A. Accili
A Conserved Domain in the NH2 Terminus Important for Assembly and Functional Expression of Pacemaker Channels
J. Biol. Chem., November 8, 2002; 277(46): 43588 - 43592.
[Abstract] [Full Text] [PDF]
D. V. Vasilyev and M. E. Barish
Postnatal Development of the Hyperpolarization-Activated Excitatory Current Ih in Mouse Hippocampal Pyramidal Neurons
J. Neurosci., October 15, 2002; 22(20): 8992 - 9004.
[Abstract] [Full Text] [PDF]
V. Macri, C. Proenza, E. Agranovich, D. Angoli, and E. A. Accili
Separable Gating Mechanisms in a Mammalian Pacemaker Channel
J. Biol. Chem., September 20, 2002; 277(39): 35939 - 35946.
[Abstract] [Full Text] [PDF]
C. Proenza, N. Tran, D. Angoli, K. Zahynacz, P. Balcar, and E. A. Accili
Different Roles for the Cyclic Nucleotide Binding Domain and Amino Terminus in Assembly and Expression of Hyperpolarization-activated, Cyclic Nucleotide-gated Channels
J. Biol. Chem., August 9, 2002; 277(33): 29634 - 29642.
[Abstract] [Full Text] [PDF]
V. Chevaleyre and P. E. Castillo
Assessing the role of Ih channels in synaptic transmission and mossy fiber LTP
PNAS, July 9, 2002; 99(14): 9538 - 9543.
[Abstract] [Full Text] [PDF]
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