A quantitative study of the Ca2+/calmodulin sensitivity of adenylyl cyclase in Aplysia, Drosophila, and rat.
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.
Yovell
Y
Y
Howard Hughes Medical Institute, Columbia University College of Physicians and Surgeons, New York.
Kandel
E R
ER
Dudai
Y
Y
Abrams
T W
TW
D000262:Adenylyl Cyclases / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001048:Aplysia / Q000201:enzymology*; D002118:Calcium / Q000494:pharmacology*; D002147:Calmodulin / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000201:enzymology; D004330:Drosophila / Q000201:enzymology*; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D002147:Calmodulin; D009419:Nerve Tissue Proteins; D000262:Adenylyl Cyclases; D008274:Magnesium; D002118:Calcium