Reexamination of the role of hyperpolarization-activated cation channels in short- and long-term plasticity at hippocampal mossy fiber synapses.
We tested a proposal that the hyperpolarization-activated cation channel (I(h) channel) is involved in the induction of short- and long-term plasticity at the hippocampal mossy fiber-CA3 synapses. Bath application of a specific I(h) channel blocker ZD 7288, at a concentration at which it blocked I(h) channels, substantially depressed mossy fiber synaptic transmission, and this inhibition was occluded by previous blockade of these channels by CsCl. In addition, ZD 7288 attenuated the amplitude of both AMPA and NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) equally and caused a coincident increase in the failure rate of single-fiber EPSCs and paired-pulse facilitation (PPF). It also blocked long-term potentiation (LTP) induction when applied before high-frequency tetanic stimulation (TS), and reversed LTP when applied afterwards. Continuous application of CsCl, which efficiently blocks I(h) channels, mimicked ZD 7288 in inhibiting LTP. Furthermore, ZD 7288 blocked both forskolin- and Sp-8-CPT-cAMPS-mediated enhancements of synaptic transmission. However, it did not affect the frequency facilitation induced by increasing the stimulus frequency from 0.05-1 Hz and the expression of the long-term depression (LTD) induced by low-frequency stimulation (LFS) or DCG-IV. Perforated patch-clamp recordings from granule cells revealed that the voltage for half-maximal activation (V(1/2)) of I(h) was significantly shifted towards the depolarizing direction following forskolin or Sp-8-CPT-cAMPS treatment. This enhanced I(h) current was not due to persistent activation of protein kinase A (PKA), because PKA inhibitor KT5720 did not abolish the difference between the activation curves. Therefore, we conclude that I(h) channels may contribute to the development and regulation of short- and long-term plasticity at the mossy fiber-CA3 synapses.
Department of Pharmacology, College of Medicine, National Cheng-Kung University, No. 1, Ta-Hsiue Road, Tainan City 701, Taiwan.
Chiung-Chun
CC
Huang
Kuei-Sen
KS
Hsu
D000818:Animals; D002227:Carbazoles; D002586:Cesium / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D054815:Cyclic Nucleotide-Gated Cation Channels; D003521:Cyclopropanes / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005110:Extracellular Space / Q000502:physiology; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000502:physiology*; D009419:Nerve Tissue Proteins; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels; D011743:Pyrimidines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
D002227:Carbazoles; D002712:Chlorides; D054815:Cyclic Nucleotide-Gated Cation Channels; D003521:Cyclopropanes; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; C578666:Hcn1 protein, mouse; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007211:Indoles; D007473:Ion Channels; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D011743:Pyrimidines; D011758:Pyrroles; C082246:ICI D2788; C082313:2-(2,3-dicarboxycyclopropyl)glycine; D002586:Cesium; C057416:KT 5720; D016291:Dizocilpine Maleate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C028019:cesium chloride; D005998:Glycine