HCN1 channels constrain DHPG-induced LTD at hippocampal Schaffer collateral-CA1 synapses.
HCN channels play a fundamental role in determining resting membrane potential and regulating synaptic function. Here, we investigated the involvement of HCN channels in basal synaptic transmission and long-term depression (LTD) at the Schaffer collateral-CA1 synapse. Bath application of the HCN channel blocker ZD7288 (10 microM) caused a significant increase in synaptic transmission that was due to an enhancement in AMPA receptor-mediated excitatory postsynaptic potentials. This enhancement was accompanied by a significant decrease in the paired-pulse ratio (PPR), suggesting a presynaptic mechanism. Experiments with the irreversible use-dependent NMDA receptor blocker MK-801 showed that ZD7288 led to an increase in glutamate release probability. LTD induced by brief application of (RS)-3,5-dihydroxyphenylglycine (DHPG, 100 microM, 10 min) was significantly enhanced when HCN channels were blocked by ZD7288 (10 microM) prior to DHPG application. Moreover, the concomitant increase in PPR after DHPG-induced LTD was significantly larger than without ZD7288 bath application. Conversely, ZD7288 application after DHPG washout did not alter DHPG-LTD. A significant enhancement of DHPG-LTD was also observed in HCN1-deficient mice as compared with wild types. However, LTD induced by low-frequency stimulation (LFS) remained unaltered in HCN1-deficient mice, suggesting a differential effect of HCN1 channels on synaptic plasticity constraining DHPG-LTD, but not LFS-LTD.
Tokay
Tursonjan
T
Institute of Physiology, University of Rostock, 18055 Rostock, Germany.
Rohde
Marco
M
Krabbe
Sabine
S
Rehberg
Mirko
M
Bender
Roland A
RA
Köhling
Rüdiger
R
Kirschstein
Timo
T
D000818:Animals; D001703:Biophysics; D056547:CA1 Region, Hippocampal / Q000166:cytology* / Q000502:physiology; D002316:Cardiotonic Agents / Q000494:pharmacology; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000172:deficiency / Q000502:physiology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D015221:Potassium Channels / Q000172:deficiency / Q000502:physiology*; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000187:drug effects* / Q000502:physiology
D002316:Cardiotonic Agents; D054815:Cyclic Nucleotide-Gated Cation Channels; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; C578666:Hcn1 protein, mouse; C578667:Hcn1 protein, rat; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D015221:Potassium Channels; D011743:Pyrimidines; D018094:Receptors, Metabotropic Glutamate; C082246:ICI D2788; D008734:Methoxyhydroxyphenylglycol; D016291:Dizocilpine Maleate; C010117:3,4-dihydroxyphenylglycol