A Quantitative Study of the Ca2+/Calmodulin Sensitivity of Adenylyl Cyclase in Aplysia, Drosophila, and Rat

Yoram Yovell, Eric R. Kandel, Yadin Dudai, Thomas W. Abrams

Research output: Contribution to journalArticlepeer-review

Abstract

Abstract: Studies in Aplysia and Drosophila have suggested that Ca2+/calmodulin‐sensitive adenylyl cyclase may act as a site of convergence for the cellular representations of the conditioned stimulus (Ca2+ influx) and unconditioned stimulus (facilitatory transmitter) during elementary associative learning. This hypothesis predicts that the rise in intracellular free Ca2+ concentration produced by spike activity during the conditioned stimulus will cause an increase in the activity of adenylyl cyclase. However, published values for the Ca2+ sensitivity of Ca2+/calmodulin‐sensitive adenylyl cyclase in mammals and in Drosophila vary widely. The difficulty in evaluating whether adenylyl cyclase would be activated by physiological elevations in intracellular Ca2+ levels is in part a consequence of the use of Ca2+/EGTA buffers, which are prone to several types of errors. Using a procedure that minimizes these errors, we have quantified the Ca2+ sensitivity of adenylyl cyclase in membranes from Aplysia, Drosophila, and rat brain with purified species‐specific calmodulins. In all three species, adenylyl cyclase was activated by an increase in free Ca2+ concentration in the range caused by spike activity. Ca2+ sensitivity was dependent on both calmodulin concentration and Mg2+ concentration. Mg2+ raised the threshold for adenylyl cyclase activation by Ca2+ but also acted synergistically with Ca2+ to activate maximally adenylyl cyclase.

Original languageEnglish
Pages (from-to)1736-1744
Number of pages9
JournalJournal of Neurochemistry
Volume59
Issue number5
DOIs
StatePublished - Nov 1992
Externally publishedYes

Keywords

  • Adenylyl cyclase
  • Aplysia
  • Associative learning
  • Calcium
  • Calmodulin
  • Classical conditioning

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Biochemistry

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