Long-lasting substance-P-mediated modulation of NMDA-induced rhythmic activity in the lamprey locomotor network involves separate RNA- and protein-synthesis-dependent stages.
Bath application of the tachykinin neuropeptide substance P (1 microm) for 10 min causes long-lasting (> 24 h) modulation of the frequency and regularity of NMDA-evoked locomotor bursts in the lamprey. The change in burst frequency has an induction phase (< 2 h), which depends on the potentiation of NMDA responses and an increase in intracellular calcium levels, and a maintenance phase (> 2 h), that is blocked by translational protein synthesis inhibitors. Here, the maintenance phase has been examined further. Unlike translation inhibitors, the transcription inhibitors actinomycin D and 5,6-dichlorobenzimidazole riboside (DRB) failed to reverse the change in burst frequency 2-3 h after substance P application, suggesting that the protein synthesized at this time does not require de novo RNA synthesis. Transcription inhibitors, however, reversed the change in burst frequency 15-24 h after substance P application, as did brefeldin A, which disrupts the Golgi complex and thus interferes with the post-translational transport of proteins. The change in burst regularity was unaffected by transcription or translation inhibitors, but was partially reversed by protein kinase A inhibitors applied 2.5-8 h after substance P. The glycoprotein synthesis inhibitor 2-deoxygalactose did not affect the changes in burst frequency or burst regularity. These results suggest that there are two phases to the maintenance of the change in burst frequency: an intermediate protein-, but not RNA-, synthesis-dependent phase, and a final RNA-synthesis-dependent phase. The change in burst regularity is protein-synthesis-independent, but may depend on activation of protein kinase A for at least 8 h after substance P application.
Parker
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D
Nobel Institute for Neurophysiology, Department of Neurosciences, Karolinska Institute, Stockholm, Sweden. david.parker@neuro.ki.se
Grillner
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S
D000818:Animals; D003609:Dactinomycin / Q000494:pharmacology; D004004:Dichlororibofuranosylbenzimidazole / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D006056:Golgi Apparatus / Q000502:physiology; D007798:Lampreys; D008297:Male; D009046:Motor Neurons / Q000737:chemistry* / Q000201:enzymology; D018377:Neurotransmitter Agents / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D010507:Periodicity; D011493:Protein Kinase C / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology*; D013550:Swimming / Q000502:physiology*
D006023:Glycoproteins; D018377:Neurotransmitter Agents; D019384:Nucleic Acid Synthesis Inhibitors; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D003609:Dactinomycin; D013373:Substance P; D004004:Dichlororibofuranosylbenzimidazole; D011493:Protein Kinase C