Adenylate cyclase system is essential for long-term facilitation at the crayfish neuromuscular junction.
Long-term facilitation (LTF), a form of synaptic plasticity demonstrated at the crayfish neuromuscular junction, is induced by tetanic stimulation and persists for hours. LTF can be divided into 2 phases: a tetanic phase, which occurs during stimulation, and a long-lasting phase, which persists after stimulation. Activators and potentiators of cAMP (forskolin and 3-isobutyl-methyl-xanthine) produce facilitation of excitatory postsynaptic potentials, which attain approximately the amplitude of the long-lasting phase of LTF but last for a shorter time. Localized presynaptic injection of a protein inhibitor ("Walsh inhibitor") specific for the cAMP-dependent protein kinase blocks the long-lasting phase of LTF at synapses near the injection site with no apparent effect on the tetanic phase. Normal LTF develops and persists at synapses of the same axon distant from the injection site. Localization of the injected inhibitor was confirmed by fluorescent tagging. Localized injection of SQ22,536, an adenylate cyclase inhibitor, also blocks the second phase of LTF near the injection site, but not at distant synapses. These experiments establish a role for adenylate cyclase activation in the long-lasting phase of LTF. The phosphatidylinositol second-messenger system is not important in LTF as inhibition of phospholipase C by injection of RA233, which blocks facilitatory effects of serotonin, does not affect any aspect of LTF.
Dixon
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Department of Physiology, University of Toronto, Ontario, Canada.
Atwood
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HL
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000502:physiology*; D000818:Animals; D003400:Astacoidea / Q000502:physiology*; D001427:Bacterial Toxins / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D009012:Mopidamol / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000502:physiology*; D010740:Phospholipases / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors; D013997:Time Factors
D000067956:Adenylyl Cyclase Inhibitors; D001427:Bacterial Toxins; D047428:Protein Kinase Inhibitors; C017759:9-(tetrahydro-2-furyl)-adenine; D005576:Colforsin; D009012:Mopidamol; D000242:Cyclic AMP; D010740:Phospholipases; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D000225:Adenine; D015056:1-Methyl-3-isobutylxanthine