Hippocampal neurons express a calcineurin-activated adenylyl cyclase.
Ca2+-stimulated adenylyl cyclases are important for several forms of neuroplasticity because they couple activity-dependent Ca2+ increases to cAMP in neurons. For example, the calmodulin-stimulated adenylyl cyclases, AC1 and AC8, are required for hippocampus-dependent memory and long-lasting long-term potentiation. To identify other mechanisms for Ca2+ stimulation of adenylyl cyclases, cultured hippocampal neurons from transgenic mice lacking both AC1 and AC8 [double knock-out (DKO) mice] were analyzed for Ca2+ stimulation of intracellular cAMP. Surprisingly, neurons from DKO mice showed significant Ca2+-stimulated cAMP accumulation that was blocked by inhibitors of calcineurin [PP2B (protein phosphatase 2B)], a Ca2+-activated protein phosphatase. Analysis of cultured neurons from calcineurin(-/-) mice confirmed that hippocampal neurons exhibit a calcineurin-dependent cAMP increase, which may contribute to some forms of neuroplasticity.
Chan
Guy C-K
GC
Department of Pharmacology, University of Washington, Seattle, Washington 98195, USA.
Tonegawa
Susumu
S
Storm
Daniel R
DR
D000262:Adenylyl Cyclases / Q000145:classification / Q000172:deficiency / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D019703:Calcineurin / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology
D004791:Enzyme Inhibitors; D011189:Potassium Chloride; D000242:Cyclic AMP; D019703:Calcineurin; D000262:Adenylyl Cyclases; D002118:Calcium