Phospholipase A2 controls the induction of short-term versus long-term depression in the cerebellar Purkinje neuron in culture.
Cerebellar long-term depression (LTD) may be reliably induced in the cultured Purkinje neuron when glutamate pulses and Purkinje neuron depolarization are applied together 6 times. When the number of these conjunctive stimuli was reduced to 2, a short-term depression (STD) lasting 20-40 min was induced in 4/12 cells. The enzyme phospholipase A2 cleaves membrane phospholipids causing liberation of free unsaturated fatty acids, which in turn synergistically activate protein kinase C when present with diacylglycerol and Ca. Application of free unsaturated fatty acids with 2 conjunctive stimuli resulted in an apparent conversion of STD cases to LTD. Application of phospholipase A2 inhibitors during 6 conjunctions converted LTD to STD. These findings suggest a model in which liberation of unsaturated fatty acids by phospholipase A2 contributes to a synergistic activation of protein kinase C, the full activation of which results in LTD induction, and the partial activation of which results in STD induction.
Linden
D J
DJ
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
D000818:Animals; D002478:Cells, Cultured; D004594:Electrophysiology; D018698:Glutamic Acid / Q000494:pharmacology; D007478:Iontophoresis; D017774:Long-Term Potentiation; D051379:Mice; D010741:Phospholipases A / Q000502:physiology*; D054467:Phospholipases A2; D011689:Purkinje Cells / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D018698:Glutamic Acid; D010741:Phospholipases A; D054467:Phospholipases A2