title: Mediation of hippocampal mossy fiber long-term potentiation by presynaptic Ih channels.
abstract: Hippocampal mossy fiber long-term potentiation (LTP) is expressed presynaptically, but the exact mechanisms remain unknown. Here, we demonstrate the involvement of the hyperpolarization-activated cation channel (Ih) in the expression of mossy fiber LTP. Established LTP was blocked and reversed by Ih channel antagonists. Whole-cell recording from granule cells revealed that repetitive stimulation causes a calcium- and Ih-dependent long-lasting depolarization mediated by protein kinase A. Depolarization at the terminals would be expected to enhance transmitter release, whereas somatic depolarization would enhance the responsiveness of granule cells to afferent input. Thus, Ih channels play an important role in the long-lasting control of transmitter release and neuronal excitability.
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143, USA.
authors.forename: Jack
authors.initials: J
authors.lastname: Mellor
authors.forename: Roger A
authors.initials: RA
authors.lastname: Nicoll
authors.forename: Dietmar
authors.initials: D
authors.lastname: Schmitz
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002586:Cesium / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D054815:Cyclic Nucleotide-Gated Cation Channels; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D066298:In Vitro Techniques; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D007546:Isoquinolines / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials; D008565:Membrane Proteins; D008959:Models, Neurological; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000502:physiology*; D009419:Nerve Tissue Proteins; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels; D017729:Presynaptic Terminals / Q000502:physiology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides; D009435:Synaptic Transmission
chemical_list: D001552:Benzazepines; D002712:Chlorides; D054815:Cyclic Nucleotide-Gated Cation Channels; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D007546:Isoquinolines; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D011743:Pyrimidines; D013449:Sulfonamides; C082246:ICI D2788; C087873:DK-AH 268; D005576:Colforsin; D002586:Cesium; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases; C106670:adenylyl cyclase 1; C028019:cesium chloride; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D011188:Potassium; D002118:Calcium