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. 1987 Oct;84(19):6948–6952. doi: 10.1073/pnas.84.19.6948

Inhibition of protein synthesis prolongs Ca2+-mediated reduction of K+ currents in molluscan neurons.

D L Alkon 1, B Bank 1, S Naito 1, C Chen 1, J Ram 1
PMCID: PMC299202  PMID: 3477819

Abstract

Elevated intracellular Ca2+ concentration within the Hermissenda type B cell has previously been shown to cause transient reduction of both the early K+ current IA and the delayed, Ca2+-dependent K+ current ICa2+-K+, a reduction that is more permanent with classical conditioning. Other earlier experiments suggested that Ca2+-mediated reduction of K+ currents initially involves the dual activation of Ca2+/calmodulin-dependent and Ca2+/lipid-dependent protein kinases. In the present study, voltage-clamp conditions that cause substantial increases in intracellular Ca2+ concentration (i.e., a Ca2+ "load") were used to produce IA and ICa2+-K+ reduction with and without the protein synthesis inhibitor anisomycin or cycloheximide or the control substance deacetylanisomycin in the bathing medium. Anisomycin (100 microM) and cycloheximide (100 microM) caused no significant change of resting membrane potential, holding current, or the non-voltage-dependent "leak" current. However, inhibition of protein synthesis prevented recovery from Ca2+-mediated K+-current reduction. This effect resembled the effect of injecting purified Ca2+-dependent kinases and was blocked by the presence of trifluoperazine in the bathing medium. Activation of protein kinase C with a water-soluble phorbol ester caused marked reduction of protein synthesis in Hermissenda neurons as monitored by two-dimensional gel electrophoresis. Synthesis of new proteins therefore may be important for reversal of initial steps during memory storage, and Ca2+-activated phosphorylation pathways may initiate long-term changes by turning off (as well as by turning on) the synthesis of particular proteins.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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