Enhancement of synaptic transmission by cyclic AMP modulation of presynaptic Ih channels.
Presynaptic activation of adenylyl cyclase and subsequent generation of cAMP represent an important mechanism in the modulation of synaptic transmission. In many cases, short- to medium-term modulation of synaptic strength by cAMP is due to activation of protein kinase A and subsequent covalent modification of presynaptic ion channels or synaptic proteins. Here we show that presynaptic cAMP generation via serotonin receptor activation directly modulated hyperpolarization-activated cation channels (Ih channels) in axons. This modulation of Ih produced an increase in synaptic strength that could not be explained solely by depolarization of the presynaptic membrane. These studies identify a mechanism by which cAMP and Ih regulate synaptic plasticity.
Beaumont
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Division of Neurobiology, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA. vahri@socrates.berkeley.edu
Zucker
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RS
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D003400:Astacoidea; D001369:Axons / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D054815:Cyclic Nucleotide-Gated Cation Channels; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D009132:Muscles / Q000166:cytology / Q000502:physiology; D009469:Neuromuscular Junction / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D015221:Potassium Channels; D017729:Presynaptic Terminals / Q000187:drug effects / Q000201:enzymology*; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D054815:Cyclic Nucleotide-Gated Cation Channels; D004791:Enzyme Inhibitors; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D010726:Phosphodiesterase Inhibitors; D015221:Potassium Channels; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines; C082246:ICI D2788; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D012701:Serotonin; C031433:8-(4-sulfophenyl)theophylline; D013806:Theophylline; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases